l
Endocrinology and Sleep State of the Art Review
Prolactin and Rapid Eye Movement Sleep Regulation
*tRachida Roky, *Ferenc ObM, Jr., §Jean-Louis Valatx, tSebastian Bredow, tJidong Fang, §Luce-Paut Pagano
and t James M. Krueger
tDepartment of Physiology and Biophysics, The University of Tennessee, Memphis, Tennessee, U.S.A.;
;f.Department of Physiology, Albert Szent-Gyorgyi Medical University, Dvm Ter Szeged, Hungary; and
§Department of Experimental Medicine, Claude Bernard University, Lyon, France
Summary:
During the past few years data have accumulated suggesting the involvement of prolactin (PRL) in rapid eye movement sleep (REMS) regulation. Pituitary PRL secretion seems to be, at least in part, sleep-dependent.
PRL is also found in the central nervous system. PRL-containing neurons in the hypothalamus project to various structures in the brain. Systemic injection ofPRL promotes REMS in rats, cats and rabbits. Intracerebroventricular injection ofPRL enhances REMS in rats. Stimulation of endogenous PRL secretion by vasoactive intestinal peptide (VIP) also promotes REMS. Immunoneutralization of blood-borne PRL slightly reduces REMS. Various obser- vations (hypoprolactinemic and hyperprolactinemic rats) indicate that PRL may act on REMS via modulating the diurnal rhythms ofREMS. It is likely that hypothalamic PRL is more important for sleep regulation than circulating PRL. Hypothalamic PRL is likely involved in the mediation of the REMS-promoting activity of VIP. We conclude that PRL has a role in REMS regulation. Key Words: Prolactin- VIP-Rapid-eye-movement sleep-Paradoxical sleep.
Sleep is regulated by the continuous dynamic inter- actions between neural circuits and humoral agents.
The concept of dynamic humoral agent influences on neural circuits, affecting multiple parameters ranging from induction of specific ion channels to neural circuit composition, has been developed for several fields in- cluding sleep regulation (see 1,2 for reviews). Almost all sleep-promoting substances are either growth fac- tors or influence growth factor production. Growth factors within the brain are thus considered an im- portant component of humoral sleep mechanisms (3).
It is hypothesized that they are crucial to a functional reorganization of neural groups involving synaptic re- sculpturing, which is considered a primordial function
Accepted for publication April 1995.
*Present address: Department of Pharmacology, Faculty of Med- icine and Pharmacology, 19 Rue Tarik Bnou Ziad, Casablanca, Mo- rocco.
Address correspondence and reprint requests to James M. Krue- ger, Department of Physiology and Biophysics, The University of Tennessee, Memphis, 894 Union Avenue, Memphis, TN 38163, U.S.A.
of sleep (1). Prolactin (PRL) is one of the growth factors that influences sleep. It is unique as a growth-sleep factor in that its primary action is to promote rapid eye movement sleep (REMS; also called paradoxical sleep). Further, it is both a circulating hormone and a neural protein, having a precise localization within the brain (see below). The findings relating PRL to sleep and the distribution and regulation of brain PRL pro- duction are recent and have primarily occurred in France, Hungary, and the U.S.A. in the laboratories of the authors. We review these findings here. We reach the conclusion that PRL is involved in REMS regu- lation although it remains to be clarified whether its effects are direct or via circadian rhythm mechanisms.
PRL and brain functions
More than 100 biological actions of PRL have ap- peared progressively during the course of evolution.
These prolactin-related functions include osmoregu- lation, reproduction (4), growth, lactation, immuno- 536
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modulation and behavior. Several of these functions involve the central nervous system (CNS). The first data concerning the effects ofPRL on brain came from experiments that demonstrated that systemically ad- ministered PRL induces changes in the firing rates of rabbit hypothalamic neurons (5). Later several studies reported that PRL, infused directly into the brain, af- fects unit activity in the neurons of the ventromedial hypothalamus (6,7), the dorsomedial hypothalamus, the arcuate nucleus (8), the preoptic area (9) and the habenula (7). The influence of PRL on tuberoinfun- dibular neurons has been intensively studied. Systemic or intracerebroventricular injection of exogenous PRL selectively increases the activity oftuberoinfundibular dopaminergic neurons (10,11). This effect is thought to be part of a negative feedback control of PRL on its own secretion. Interestingly, other studies demon- strated that PRL affects dopamine secretion in extra- hypothalamic areas. For example, PRL increases the extracellular dopamine in the accumbens nucleus (12) and increases the density of striatal dopamine receptors (13). Moreover, PRL modulates the cholinergic turn- over in the hippocampus and in the striatum, where dopaminergic neurons exert a tonic inhibitory influ- ence (l0). Those findings may explain some of the behavioral responses induced by PRL injection, such as grooming and yawning behavior, which are medi- ated by dopaminergic transmission in the brain (14).
Like dopamine, PRL also increases the level of gam- ma-aminobutyric acid (GABA) in areas related to PRL feedback on its own secretion (15) as well as other areas in brain not involved in PRL regulation, such as the substantia nigra (16). Moreover, PRL affects other neu- ropeptides in the brain such as vasoactive intestinal peptide (VIP), oxytocin and proopiomelanocorticotro- pin (17,18). The central effects of PRL are mediated via specific brain receptors. The PRL receptor local- ization has been studied in neural tissue; using binding techniques, the presence of PRL receptors in the cho- roid plexus and the hypothalamus was demonstrated (19-25). More recently, binding sites for PRL in dis- tinct nuclei were described by immunohistochemistry using monoclonal antibodies (26). In that study PRL receptor immunoreactivity was observed in the supra- chiasmatic, supraoptic, and paraventricular nuclei of the hypothalamus, preoptic area, cerebral cortex, hip- pocampus, amygdala formation, thalamus, habenula, substantia nigra and the choroid plexus. Generally, PRL receptors were observed in areas that receive PRL fibers, although mismatches were also observed (26).
Is PRL secretion related to sleep?
The sleep-related increases in plasma PRL concen- trations were discovered in humans (27,28). PRL con-
centration rises soon after sleep onset, and maximal values are observed in the early morning hours. Results from experiments using shifting bedtimes or sleep de- privation confirmed the association between sleep and PRL secretion (29,30). Decreased dopaminergic inhi- bition of pituitary PRL secretion has been suggested as the cause of the enhanced PRL secretion during non- rapid eye movement sleep (NREMS) (29). Neverthe- less, whereas they confirmed the sleep-related PRL se- cretion, these studies also revealed that regulation of PRL secretion has a circadian component independent of sleep (31). PRL secretion is suppressed during sleep deprivation when the subjects are exposed to a light environment, but plasma PRL concentration increases during sleep deprivation in a dark environment (32).
Bright light at night elicits suppression of melatonin release, followed by decreases in plasma PRL concen- tration (33). Melatonin modulates PRL secretion in rats (34) and hamsters (35). Melatonin, therefore, might be involved in the circadian component of PRL reg- ulation.
Although the sleep-associated PRL secretion is widely accepted in humans, it is a subject of controversy whether PRL release varies with the sleep cycle. A strong correlation between plasma PRL concentration and sleep cycles was originally suggested, with high and low concentrations of PRL during NREMS and REMS, respectively (36). Subsequent studies, howev- er, failed to confirm this relationship (37). Neverthe- less, the onset ofREMS is rarely associated with rising plasma concentrations of anterior pituitary hormones in general, and in particular, with the ascending phase ofPRL pulses (38). Calculation of secretion rates con- firmed that REMS onset is linked to decreased PRL release (29).
To our knowledge, relationships between sleep and variations in plasma PRL concentrations have not been studied in rats. Maximum plasma PRL concentrations occur in the dark period, when the rats are active, in Sprague-Dawley and Wistar rats (39-41). However, this diurnal pattern may vary with the strain of the rats. Thus, major PRL pulses are observed at the end of the light period in black-hooked/Ztn rats (40).
Although intrahypothalamic PRL might be more important for sleep regulation than pituitary PRL (see below), it is not known if intracerebral PRL varies with sleep or the diurnal cycle.
PRL in the brain: localization, distribution and regulation
Fuxe et al. (42) were the first to report a PRL-like immunoreactivity (PRL-LIR) in rat brain; using an- tibodies to rat PRL these immunohistochemical stud- ies localized PRL to the hypothalmus and preoptic
Sleep. Vol. 18. No.7. 1995
area. Signals were obtained in nerve fibers of the ar- cuate nucleus. the dorsomedial hypothalamic nucleus and the peri ventricular regions of the hypothalamus and preoptic area. Toubeau et al. (43) expanded these studies again using immunocytochemical methods.
These authors localized PRL-immunoreactive neurons within the arcuate, ventromedial. premamillary, su- praoptic paraventricular nuclei of the hypothalamus.
Further, they also found immunoreactive fibers after treatment with colchicine in the amygdala, the locus coeruleus and around the nuclei of the vagus and hy- poglossal nerves. More recently, several additional re- ports describe the distribution of PRL in mammalian brain; some of these included the use of radioimmu- noassay (RIA) (see 44 for review). Most of these studies concentrated on the hypothalamus. However, depend- ing on what technique or antibody was used, staining was also observed in other brain areas. e.g. perifornical region and the bed nucleus of stria terminalis (45), the cerebral cortex and brainstem (46). De Vito (47) ex- tracted PRL-LIR from the cerebellum and hippocam- pus and analyzed the concentrations by RIA. The latest in this series is the report by Paut-Pagano et al. (48), who described the distribution of a PRL-LIR in the rat eNS using a specific antiserum to ovine PRL. The authors found the PRL-LIR exclusively in the lateral hypothalamic area, whereas other parts of the brain remained unstained. The stained hypothalamic neu- rons, however, project into many brain regions.
The immunohistochemical studies were corrobo- rated over the past few years by reports that described the distribution of PRL mRNA in normal brain. In 1984, Schachter et al. (49) were the first to show the existence of PRL mRNA in the hypothalamus using purified hypothalamic poly A
t-RNA in classical Northern analyses. Using the reverse transcriptase- polymerase chain reaction technique, several groups have now confirmed and extended that result by de- tecting PRL mRNA with varying intensities in the hypothalamus and several other areas of normal rat brain, including the cerebellum, caudate, brain stem, amygdala, thalamus and cortex (44.50.51,52). The message from brain seems to be identical to that of the pituitary (53). Emanuele et al. (44), however, reported the presence of a shorter, alternatively spliced mRNA for PRL lacking exon 4. The presence ofa smaller PRL protein in brain has not been confirmed thus far, and its function is unknown. though several forms of pro- teolyically cleaved PRL are known to exist in the pi- tuitary gland (54.55) and in brain (56). However, it is now safe to conclude that brain is able to synthesize bioactive PRL.
Little is known about the regulation of the PRL gene in extrahypophyseal tissues. Hypophysectomized rats do not express the PRL gene in the hypothalamus,
Sleep. Vol. 18. No.7. 1995
amygdala, caudate and brain stem; however, testos- terone treatment partially restores the transcription, mainly in the caudate and brain stem, in the form of the alternatively spliced mRNA (44). It should be not- ed. however, that the PRL-LIR is still detectable in brain of hypophysectomized rats (48,57.58). Further, there is evidence that the pituitary-specific transcrip- tion factor Pit-IIGHF, which plays an important part in the regulation of pituitary expressed PRL-mRNA (59,60), seems to be absent in brain (44). Given the fact that the expression of the PRL promoter is regu- lated by a number of different polypeptide and steroid hormones, acting through two distinct regulatory regions approximately 1,500 bp apart (61-63), these data would support the hypothesis of a different PRL regulation in the brain (64).
PRL promotes REMS
The REMS-promoting activity of PRL has been demonstrated in three species: the cat, rabbit and rat.
jouvet et al. (65) noticed that systemic administration of PRL enhanced REMS in cats whose brain stem was transected at the level of the pons and the hypophysis was lesioned. Subsequently. Obitl et al. (66) reported that subcutaneous injection of PRL selectively stim- ulated REMS in rabbits. Finally, Roky et al. (67,68) demonstrated increases in REMS in response to sys- temic or intracerebral (intrahypothalamic) injection of PRL in the rat. Two features of the promotion ofREMS by PRL might be particularly important to understand the mechanism of the effect of PRL. First, enhance- ments in REMS occur 1-2 hours following the injection of PRL in both rabbits (66) and rats (68). Second.
experiments in rats demonstrate that the effects ofPRL on sleep vary with the diurnal cycle. Only PRL ad- ministered during the light period stimulates REMS.
whereas PRL injected at night inhibits REMS (67).
In addition to the direct sleep-inducing effects of exogenous PRL, some observations suggest that en- dogenous PRL is in fact involved in the regulation of REMS. Obal et al. (69) used systemic VIP injection to stimulate pituitary PRL secretion. Systemic VIP ad- ministration elicited increases in REMS during the light cycle in the rat. The REMS-promoting activity of sys- temic VIP was inhibited by immunoneutralization of the circulating PRL in the rat. Systemic administration of the PRL-antiserum per se resulted in a slight and selective suppression ofREMS (70). These findings are supported by recent observations in human subjects (71). The effects on sleep and hormones of four i.v.
bolus injections of VIP (4 x 10f.Lgor4 x 50f.Lg)were determined. The small dose failed to stimulate PRL (in fact, PRL decreased) and did not alter sleep. The high dose stimulated both PRL and REMS. Interest-
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ingly, systemic VIP also enhanced the duration of the sleep cycles. Finally, intrahypothalamic injection of PRL antiserum also decreased REMS (68). It is to be noted, however, that the effects of intrahypothalamic PRL antiserum on sleep were tested at night, i.e. during the period of the day when intrahypothalamic PRL also inhibited REMS. This inhibitory effect ofPRL on REMS could be exerted via auto receptors localized on PRL neurons, because PRL receptors were observed in the same area that contains the PRL neurons (la- terodorsal hypothalamus) (26,48). The sensitivity of the receptors could be different during the dark and light periods.
It is possible that the intracerebral PRL is much more important than pituitary PRL for the regulation of REMS. The relative unimportance of the pituitary PRL is indicated by the finding that suppression of normal pituitary PRL secretion has little effect on REMS (70). Bloodborne PRL can enter the CNS via a specific transport mechanism residing in the choroid plexus (72). It is possible therefore that circulating PRL acts on the same receptors in the brain that are nor- mally exposed to intraneuronal PRL produced by nerve cells in the hypothalamus.
The mechanism of the PRL-induced stimulation of REMS is not known. The long latency of the effect suggests that it is not a direct triggering action. Instead, PRL may modulate neuronal transmission involved in the generation of REMS. The circadian variations in the PRL effects on sleep and the observations in the hypoprolactinemic mutant rats (73) suggest that PRL is implicated in the circadian regulation of REMS (see below). PRL might also influence sleep via some in- tracerebral or systemic metabolic actions. Nagy and Berczi (74) recognized that PRL is required for survival in the rat, and therefore, variations in PRL concentra- tions may indirectly influence sleep. Finally, the sleep studies with PRL to date were carried out in male rats and rabbits. It is not clear how PRL affects sleep in females, which have more robust PRL production than males. Also, the reports cited above describe sleep fol- lowing acute experimental manipulation of PRL. It is not clear how chronic physiological (e.g. lactation) al- terations in PRL concentration affect sleep.
The hypnogenic effect of VIP and structurally related peptides may be mediated via PRL
VIP, pituitary adenyl ate cyclase-activating peptide (PACAP), peptide histidine methionine (PHM), pep- tide histidine isoleucine (PHI) and growth hormone- releasing hormone (GHRH) belong to the secretin- glucagon peptide family. VIP, PACAP, PHI, PHM and GHRH are found in the brain: some, e.g. VIP and PHI,
often colocalize with each other and arc rather wide- spread within the CNS (75). Specific receptors for some of these peptides have also been described in brain, although cross-reaction between one peptide and the receptor of another can occur. For example, there are two types of high-affinity PACAP receptors: the type I receptor is specific for PAC AP, though the type II receptor is thought to be equivalent to the VIP receptor (76). Similarly, PHI and GHRH can act on VIP re- ceptors (77).
Reports from several laboratories suggest that both central (66,78-82) and systemic (69) administration of VIP enhances REMS. In fact, VIP is one of the best characterized sleep factors (see 2 for review). There are also reports that PHM (66), GHRH (83) and PACAP (84) induce REMS. The REMS-promoting activity of these peptides could be mediated in some species through their actions on VIP receptors. as suggested above. Additional evidence also supports the notion that VIP is involved in physiological REMS regulation.
Thus, Drucker-Colin et al. have shown that anti-VIP antibodies neutralize the REMS-promoting substance that accumulated in cerebrospinal fluid (CSF) of sleep- deprived cats (85). Subsequently. this group directly demonstrated an increase of VIP in CSF obtained from REMS-deprived cats (86). Others showed that central administration of anti-VIP antibodies (79) or a VIP competitive antagonist (87) induces selective REMS inhibition.
Despite the strong evidence for VIP involvement in REMS regulation. the mechanism is not clear. The effects of VIP on REMS do not appear to be mediated by serotonin or acetylcholine (79.85). In fact. acetyl- choline may even release VIP (88). Important for this review is that VIP is a known releasing factor for pi- tuitary PRL, acting at the levels of both the hypo- thalamus and the pituitary gland (89-93). Somnogenic doses of VIP and PACAP also induce hypothalamic production ofPRL mRNA (52). Further evidence sug- gesting the involvement of PRL in the REMS pro- moting effects of VIP is the observation that anti-PRL antibodies block VIP-enhanced REMS (68). It is noted, however, that exogenous VIP stimulates both REMS and intracerebral PRL during the dark period of the day, and this finding is in conflict with the circadian variations in REMS-promoting activity of PRL.
The involvement of PRL in the circadian rhythms of sleep
A recessive mutation leading to a defIcit in blood PRL in the Sprague-Dawley strain was discovered at the Institut Pasteur de Lyon (IPL). Through selective breeding, a new strain called "IPL" was established.
These rats are hairless, and the females are unable to
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lactate. The endocrine status of these mutant rats was studied by Cohen el al. (94). Briefly, blood prolactin is reduced by 50%. There is also a significant reduction in luteinizing hormone (LH), follicle-stimulating hor- mone (FSH) and testosterone levels. Moreover, the night peak of melatonin content in the pineal gland is decreased by 50%.
In the first experiments using the IPL strain a 34%
decrease in REMS duration was reported; this decrease occurred mainly during the light period, leading to a trend to reverse the circadian rhythm. However. re- cordings were done at room temperature (24° ± 1°C).
For these hairless rats, this temperature is a cold en- vironment. Indeed, the rats had an increase in heart rate and food intake, both characteristic of acclimation to cold exposure. Moreover. it is well known that cold exposure decreases the duration of REMS. In a warm environment (30°C), sleep durations in the IPL strain reached the level of nonmutant rats. The circadian sleep-wake rhythm, however, was altered and was characterized by desynchronization between the slow- wave sleep (SWS) and REMS rhythms. The circadian SWS rhythm remained unchanged (1/3 during night.
2/3 during day), whereas the circadian REMS rhythm was reversed (3/4 during night 1/4 during day). It was the first time that such a spontaneous desynchroni- zation was observed. This finding confirms previous lesion experiments (pinealectomy, paraventricular nu- cleus) (95,96) that indicated that there are at least two regulatory mechanisms for SWS and REMS rhythms.
Recently, chronic administration ofPRL by grafting a PRL-producing tumor (prolactinoma) under the kid- ney capsule provoked an unexpected result. One month after graft, progressively high levels of blood PRL were accompanied by a progressive desynchronization of SWS and REMS rhythms similar to that seen in the IPL mutant rats. Such a finding suggests that the al- teration of the REMS rhythm is actually due to an increase in brain PRL levels. In the grafted rats, CSF levels represent 5-10% of the serum level (Valatx, per- sonal communication).
Given that hypophysectomy does not cause such a desynchronization, pituitary PRL does not appear re- sponsible for this alteration. These results suggest that in the mutant rats either PRL neurons could be hy- peractive or PRL receptors more sensitive. Very re- cently, Roky et al. (26) showed that PRL receptors were numerous in the suprachiasmatic nucleus (SCN). How- ever, it remains to be demonstrated that a high level ofPRL in the SCN could reverse the REM sleep rhythm.
Conclusion
It is probably safe to conclude within the context of the humoral regulation of sleep that PRL is involved
Sleep. Vol. 18, No.7, 1995
in sleep regulation. Several laboratories using a diverse range of experimental approaches have reached this conclusion. However, we hope that the present dis- cussion has emphasized that any sleep factor should be considered within the context of its immediate class of compounds such as its receptors, inducers, etc. Sec- ond, sleep factors should be considered within the con- text of how physiological variables interact with them.
Finally, how sleep factors are interlinked with other sleep factors (see 2,3 for reviews) and how they operate within the brain to regulate sleep need consideration.
As our knowledge of the mechanisms by which PRL affects REMS increases, our knowledge of the func- tional organization of brain and even the function of sleep should be greatly enhanced.
Acknowledgements: This work was supported in part by grants from the National Institutes of Health (U .s.A.) (NS-
27250 and NS-25378), Institut National de la Saute et de la Recherche Mcdicale (INSERM U52) and Centre National de la Recherche Scientifique (CNRS, URA 1195) France.
REFERENCES
I. Krueger JM. Obal F J r. A neuronal group theory of sleep func- tion.
J Slecp Res 1993:2:63-9.2. Krueger JM, Obal F Jr. Sleep Factors. In: Saunders NA. Sullivan CEo eds. ,';'Iecp and hl'eathing. New York: Marcel Dekker. Inc.
1994:79-112.
3. Krueger JM. Ob<'!1 F Jr. Growth hormone-releasing hormone and interleukin-I in sleep regulation.
F~SEBJ 1993;7:645-52.
4. Buntin JD. Prolactin-brain interactions and reproductive func- tion. Am 7001 1993:33:229-43.
5. Clemens JA. Gallo RV. Whitmoyer DJ. Sawyer CH. Prolactin responsive neurons in the rabbit hypothalamus. Brain Res 1971:
25:371-9.
6. Yamada Y. Effects of iontophoretic ally-applied prolactin on unit activity of the rat bran . .\'eurocndocrill%gy 1
<n 5: 18:263-71.7. Chan A, Dudley CA. Moss RL Action of prolactin. dopamine and LHRH on ventromedial hypothalamic neurons as a func- tion of ovarian homones. ;\'elll'Ocndocrinolog)' 1983:36:397-403.
8. Haskins JT. Moss RL Differential effects of morphine. dopa- mine and prolactin administered iontophoretically on arcuate- ventromedial hypothalamic neurons. Brain Res 1983:268: 185-8.
9. Poulain p. Carette B. Actions of iontophoretically applied pro- lactin on septal. preoptic neurons in the guinea pig. Brain Res
1976; 116: 172-6.
10. Moore KE, Demarest KT. Johnston CA. Influence of prolactin on dopaminergic neuronal systems in the hypothalamus. Fed PI'OC 1980:39:2912-6.
II. Demarest KT. Moore KE. Riegle GD. Responsiveness of tub- eroinfundibular dopamine neurons in the aged female rat to the stimulatory actions of prolactin. ,\'cUl'OelldocriIlOlogy 1987:45:
227-32.
12. Gonzalez-Mora JL Guadalupe T. Mas M. In vivo voltammetry study of the modulatory action of prolactin on the mesolimbic dopaminergic system. Brain Res Bull 1990:25:729-33.
13. Hruska RE. Pitman KT. Silbergeld EK. Ludmer LM. Prolactin increases the density of striatal dopamine receptors in normal and hypophysecton;ized male rats. Liti'Sci 1982;30:547-53.
14. Drago F. Van Ree JM. Bohus B. Wied DE. Endogenous hyper- prolactinaemia enhances amphetamine and apomorphine-in- duced stereotypy. EliI' J Phal'll1acol198 1:72:249-53.
15. Felman K. Tappaz M. GABAergic biochemical parameters of
Downloaded from https://academic.oup.com/sleep/article-abstract/18/7/536/2749670
the tuberoinfundibular neurons following chronic hyperprolac- tinemia. Neuroendocrinology 1989;49:580-5.
16. Nicoletti F, Di Giorgio RM, Patti F, et al. Influence of hyper- prolactinemia induced by adenopituitary transplantation under the kidney capsule on the glutamic acid decarboxylase activity in various brain regions. Arch lnt Pharmacodyn 1981 ;249:153-7.
17. Sarkar DK. Evidence for prolactin feedback actions on hypo- thalamic oxytocin, vasoactive intestinal peptide and dopamine secretion. Neuroendocrinology 1989;49:520-4.
18. Tong Y, Pelletier G. Prolactin regulation of pro-opiomelano- cortin gene expression in the arcuate nucleus of the rat hypo- thalamus. Neuroendocrinology 1992;56: 561-5.
19. Brooks PJ, Funabashi T, Kieopoulos SP, Mobbs CV, PfaffDW.
Prolactin receptor messenger RNA is synthesized by the epi- thelial cells of the choroid plexus. Mol Brain Res 1992; 16: 163-7.
20. Di Carlo R, Muccioli R, Papotti MG, Bussalati G. Character- ization of prolactin receptor in human brain and choroid plexus.
Brain Res 1992;570:341-6.
21. Chiu S, Koos RD, Wise PM. Detection of prolactin receptor (PRL-R) mRNA in the rat hypothalamus and pituitary gland.
Endocrinology 1992;130:1747-52.
22. Crumeyrolle-Arias M, Latouche J, Jammes H, et al. Prolactin receptors in the rat hypothalamus: autoradiographic localization and characterization. Neuroendocrinology 1993;57:457-66.
23. Fechner JH Jr, Buntin JD. Localization of prolactin binding sites in ring dove brain by quantitative autoradiography. Brain Res 1989;487:245-254.
24. Muccioli G, Gh C, Di Carlo R. Distribution and characterization of prolactin binding sites in the male and female rat brain: effects of hypophysectomy and ovariectomy. Neuroendocrinology 1991;
53:47-53.
25. Walsh RJ, Posner BI, Kapriwa BM, Brawer JR. Prolactin bind- ing sites in the rat brain. Science 1978;201:1041-2.
26. Roky R, Paut-Pagano L, Kitahama K, Valatx JL, Kelly PA, Jouvet M. Distribution of prolactin receptors in the rat fore- brain: immunohistochemical study. Neuroendocrinology 1995 (in press).
27. Sassin JF, Frantz AG, Kapen S, Weitzman ED. The nocturnal rise of human prolactin is dependent on sleep. J Clin Endocrinol Metab 1973;37:436-40.
28. Parker DC, Rossman LG, Vanderlaan EF. Sleep-related, nyc- tohemeral and briefly episodic variation in human plasma pro- lactin concentrations. J Clin Endocrinol Metab 1973;36: 1119- 22.
29. Spiegel K, Follenius M, Simon C, Saini J, Ehrhart J, Branden- berger G. Prolactin secretion and sleep. Sleep 1994;17:20-7.
30. Desir D, Van Cauter E, L'Hermite M, et al. Effects of "jet lag"
on hormonal patterns. III. Demonstration of an intrinsic cir- cadian rhythmicity in plasma prolactin. J Clin Endocrinol Metab 1982;55:849-57.
31. Van Cauter E. Diurnal and ultradian rhythms in human en- docrine function: a mini review. Horm Res 1990;34:45-53.
32. Okatani Y, Sagara Y. Role of melatonin in nocturnal prolactin secretion in women with normoprolactinemia and mild hyper- prolactinemia. Am J Obstet GynecoI1993;168:854-61.
33. Bispink G, Zimmerman R, Weise HC, Leidenberger F. Influence of melatonin on the sleep-independent component of prolactin secretion. J Pineal Res 1990;8:97-106.
34. Moreno ML, Villanua MA, Esquifino AL. Serum prolactin and luteinizing hormone levels and the activities of hypothalamic monoamine oxidase A and Band phenylethanolamine-N-meth- yl transferase are changed during sexual maturation in male rats treated neonatally with melatonin. J Pineal Res 1992; 13: 167- 73.
35. Petterborg LJ, Richardson BA, Vaughan MK, Reiter RJ. Acute effects of a single afternoon melatonin injection on LH, prolac- tin, and pineal melatonin titers in the Syrian hamster. J Neural Transm (Austria) 1984;59:299-307.
36. Parker DC, Rossman LG, Vanderlaan EF. Relation of sleep- entrained human prolactin release to REM-non REM cycles.
JClin Endocrinol Metab 1974;38:646-51.
37. Van Cauter E, Desir D, Refetoff S, et al. The relationship be- tween episodic variations of plasma prolactin and REM-non-
REM cyclicity is an artifact. J Clin Endocrinol Metab 1982;54:
70-5.
38. Follenius M, Brandenberger G, Simon C, Schlienger JL. REM sleep in humans begins during decreased secretory activity of the anterior pituitary. Sleep 1988; II :546-55.
39. Dunn JD, Hess M, Johnson DC. Effect of thyroidectomy on rhythmic gonadotropin release (39135). Proc Soc Exp Bioi Med 1976;151:22-7.
40. Wong C-C, Dahler K-D, Geerling H, von zur Miihlen A. Influ- ence of age, strain and season on circadian periodicity of pitu- itary, gonadal and adrenal hormones in the serum of male lab- oratory rats. Horm Res 1983;17:202-15.
41. Laakso M-L, Porkka-Heiskanen T, Alila A, Peder M, Johansson G. Twenty-four-hour patterns of pineal melatonin and pituitary and plasma prolactin in male rats under 'natural' and artificial lighting conditions. Neuroendocrinology 1988;48:308-13.
42. Fuxe K, Hakfelt T, Eneroth P, Gustafsson J-A, Skett P. Pro- lactin-like immunoreactivity: localization in nerve terminalis of rat hypothalamus. Science 1977; 196:899-900.
43. Toubeau G, Desclin J, Parmentier M, Pasteels JL. Cellular lo- calization of a prolactin-like antigen in the rat brain.
J Endo-crinoI1979;83:261-6.
44. Emanuele NV, Jurgens JK, Halloran MM, Tentler JJ, Lawrence AM, Kelley MR. The rat prolactin gene is expressed in brain tissue: detection of normal and alternatively spliced prolactin messenger RNA. Mol Endocrinol 1992;6:35-42.
45. Siaud P, Manzoni 0, Balmefrezol M, Barbanel G, Assenmacher I, Alonso TG. The organization of prolactin-like immunoreac- tive neurons in the rat central nervous system: light and electon- microscropic immunocytochemical studies. Cell Tissue Res 1989;
255:107-15.
46. Harlan RE, Shivers BD, Fox SR, Kaplove KA, Schachter BS, Pfaff DW. Distribution and partial characterization of immu- noreactive prolactin in the rat brain. Neuroendocrinology 1989;
49:7-22.
47. De Vito WJ. Distribution of immunreactive prolactin in the male and female rat brain: effects of hypophysectomy and in- traventricular administration of colchicine. Neuroendocrinology 1988;47:284-9.
48. Paut-Pagano L, Roky R, Valatx J-L, Kitahama K, Jouvet M.
Anatomical distribution of prolactin-like immunoreactivity in the rat brain. Neuroendocrinology 1993;58:682-95.
49. Schachter BS, Durgerian S, Harlan RE, PfaffPW, Shivers BD.
Prolactin mRNA exists in rat hypothalamus. Endocrinology 1984;
114: 1947-9.
50. Valatx J-L, Paut-Pagano L, Fevre-Montagne M, Dumas-Milne- Edwards J-B, Jouvet M. Mise en evidence d'ARN messagers de la prolactine apres amplification dans Ie cerveau du rat. C R Acad
SciParis 1992;315:295-301.
51. Fields K, Kulig E, Lloyd RV. Detection of prolactin messenger RNA in mammary and other normal and neoplastic tissues by polymerase chain reaction. Lab Invest 1993;68:354-60.
52. Bredow S, Kacs6h B, Obal F Jr, Fang J, Krueger JM. Increase of prolactin mRNA in the rat hypothalamus after intracerebro- ventricular injection of VIP or PACAP. Brain Res 1994;660:
301-8.
53. Wilson DM III, Emanuele NV, Jurgens JK, Kelley MR. Pro- lactin message in the brain and pituitary of adult male rats is identical: PCR cloning and sequencing of hypothalamic prolac- tin eDNA from intact and hypophysectomized adult male rats.
Endocrinology 1992; 131 :2488-90.
54. Powers CA, Hatala MA. Prolactin proteolysis by glandular kal- likrein: in vitro reaction requirements and cleavage sites and detection of processed prolactin in vivo. Endocrinology 1990;
127:1916-27.
55. Ho TWe, Balden E, Chao J, Walker AM. Prolactin processing by kallikrein: production of the 21-23.5K prolactin-like mole- cules and inferences about prolactin storage in mature secretory granules. Endocrinology 1991; 121: 184-192.
56. De Vito WJ, Avakian C, Stone C. Proteolytic modification of prolactin by the female rat brain. Neuroendocrinology 1992;56:
597-603.
57. Emanuele NV, Metcalfe L, Wallock L, et al. Hypothalamic pro-
Sleep. Vol. 18. No.7. 1995I
l
lactin: characterization by radioimmunoassay and bioassay and response to hypophysectomy and restraint stress. Neuroendo- crinology 1986;44:217-21.
58. Barbanel G, Ixart G, Arancibia S, Assenmacker
I.Probable extrapituitary source of the immunoreactive prolactin measured in the cerebrospinal fluid of unanesthetized rats by push-pull cannulation of the 3rd ventricle. Neuroendocrinology 1986;43:
476-82.
59. McCormick A, Brady H, Theill LE, Karin M. Regulation of the pituitary-specific homeobox gene GHF 1 by cell-autonomous and environmental cues. Nature 1990;345:829-32.
60. Castrillo J-L, Theil! LE, Karin M. Function of the homeodomain protein GHF 1 in pituitary cell proliferation. Science 1991;253:
197-9.
61. Delidow BC, Billos WM, Agarwal P, White BA. Inhibition of prolactin gene transcription by transforming growth
factor-~in GH3 cells. Mol EndocrinaI1991;5:1716-22.
62. Berwaer M, Peers B, NaIda AM, et al. Thyrotropin-releasing hormone and epidermal growth factor induce human prolactin expression via identical multiple cis elements. Mol Cell Endo- crino/1993;92:1-7.
63. Cullen KE, Kladde MP, Seyfred MA. Interaction between tran- scription regulatory regions of prolactin chromatin. Science 1993;
261:203-6.
64. Emanuele NV, Metcalfe L, Wallock L, et al. Extrahypothalamic brain prolactin: characterization and evidence for independence from pituitary prolactin. Brain Res 1987;421:255-62.
65. Jouvet M, Buda C, Cespuglio R, et al. Hypnogenic effects of some hypothalamo-pituitary peptides. Clin Neuropharmacol
1986; 9, Suppl 4:465-467.
66. OMI F Jr, Opp M, Cady AB, Johannsen L, Krueger JM. Pro- lactin, vasoactive intestinal peptide, and peptide histidine me- thionine elicit selective increases in REM sleep in rabbits. Brain Res 1989;490:292-300.
67. Roky R, Valatx J-L, Jouvet M. Effect of prolactin on the sleep- wake cycle in the rat. Neurosci Lett 1993; 156: 117-20.
68. Roky R, Valatx J-L, Paut-Pagano L, Jouvet M. Hypothalamic injection of prolactin or its antibody alters the rat sleep-wake cycle. Physiol Behav 1994;55: 1015-9.
69. Obal F Jr, Payne L, Kacs6h B, et al. Involvement of prolactin in the REM sleep-promoting activity of systemic vasoactive intestinal peptide (VIP). Brain Res 1994;645:143-9.
70. OMI Jr F, Kacs6h B, AlfOldi P, et al. Antiserum to prolactin decreases rapid eye movement sleep (REM sleep) in the male rat. Physiol Behav 1992;52: 1063-8.
71. Murck H, Schier T, Colla-Muller M, et al. Vasoaktives intes- tin ales polipeptid (VIP) reguliert den NonREM-REM-Zyklus des Menschen-eine schlafendokrinologische studie. Fort- schritte der Neurologie Psychiatrie 1994;62: 1 04-5.
72. Walsh RJ, Slaby FJ, Posner BI. A receptor-mediated mechanism for the transport of prolactin from blood to cerebrospinal fluid.
Endocrinology 1987; 120: 1846-50.
73. Valatx J-L, Jouvet M. Les rythmes circadiens du sommeillent et du sommeil paradoxal sont en opposition de phase chez les rat atriches hypoprolactinemiques. C R Acad Sci (Paris) 1988;
307:789-94.
74. Nagy E, Berczi I. Hypophysectomized rats depend on residual prolactin for survival. Endocrinology 1991;128:2776-84.
75. Chiristofides ND, Polak JM, Bloom SR. Studies on the distri- bution of PHI in mammals. Peptides 1984;5:261-6.
76. Shivers B, Gores T, Gottschall P, Arimura A. Two high affinity binding sites for pituitary adenylate cyclase-activating polypep- tide have different tissue distributions. Endocrinology 1991; 128:
3055-65.
77. Laburthe M, Amiranoff B, Boige N, Rouyer-Fessard C, Tate- moto K, Moroder L. Introduction of GRF with VIP receptors and stimulation of adenyl ate cyclase in rat and human intestinal epithelial membranes. FEBS Lett 1983; 159:89-92.
Sleep. Vol. 18. No.7. 1995
78. Obal F Jr, Sary G, AlfOldi P, Rubicsek G, ObM F. Vasoactive intestinal polypeptide promotes sleep without effects on brain temperature in rats at night. Neurosci Lett 1986;64:236-40.
79. Riou F, Cespuglio R, Jouvet M. Endogenous peptides and sleep in the rat: III. The hypnogenic properties of vasoactive intestinal peptide. Neuropeptides 1982;2:265-77.
80. Drucker-Colin R, Bernal-Pedraza J, Fernandez-Cancino F, Oks- enberg A. Is vasoactive intestinal polypeptide (VIP) a sleep fac- tor? Peptides 1984;5:837-40.
81. Kruisbrink J, Mirmiran A, van der Woude TP, Boer GJ. Effects of enhanced cerebrospinal fluid levels of vasopressin, vaso- pressin antagonist or vasoactive intestinal polypeptide on cir- cadian sleep-wake rhythm in the rat. Brain Res 1987;419:76- 86.
82. Prospero-Garcia
0,Morales M, Arankowsky-Sandoval G, Drucker-Colin R. Vasoactive intestinal polypeptide (VIP) and cerebrospinal fluid (CSF) of sleep-deprived cats restores REM sleep in insomniac recipients. Brain Res 1986;385: 169-73.
83. OMI F Jr, AlfOldi P, Cady AB, Johannsen L, Sary G, Krueger JM. Growth hormone-releasing factor enhances sleep in rats and rabbits. Am J PhysioI1988;255:R31O-6.
84. Fang J, Payne L, Krueger JM. Effect of pituitary adenylate cy- clase activating polypeptide on sleep in rats. Sleep Res 1993;22:
517.
85. Drucker-Colin R, Prospero-Garcia
0,Arankowsky-Sandoval G, Perez-Montfort R. Gastropancreatic peptides and sensory stimuli as REM sleep factors. In: Inoue S, Schneider-Helmert D, eds. Sleep peptides: basic and clinical approaches. Tokyo:
Japan Scientific Society and Springer, 1988:73-94.
86. Jimenez-Anguiano A, Baez-Saldana A, Drucker-Colin R. Ce- rebrospinal fluid (CSF) extracted immediately after REM sleep deprivation prevents REM rebound and contains vasoactive intestinal peptide (VIP). Brain Res 1993;631 :345-8.
87. Mirmiran M, Kruisbrink J, Bos NPA, Van der WerfD, Boer GJ. Decrease of rapid-eye-movement sleep in the light by in- traventicular application of a VIP-antagonist in the rat. Brain Res 1988;458:192-4.
88. Kaji H, Chihara K, Minamitani N, Kodama H, Yanaihara N, Fujita T. Release of vasoactive intestinal polypeptide into the cerebrospinal fluid of the fourth ventricle of the rat: involvement of cholinergic mechanism. Brain Res 1983;269:303-10.
89. Abe H, Engler D, Moltich ME, Bollinger-Gruber J, Reichlin S.
Vasoactive intestinal peptide is a physiological mediator of pro- lactin release in the rat. Endocrinology 1985;/16:1383-90.
90. Hagen TC, Arnaout MA, Scherzer WJ, Martinson DR, Garth- waite TL. Antisera to vasoactive intestinal peptide inhibit basal prolactin release from dispersed anterior pituitary cells. Neu- roendocrinology 1986;43:641-5.
91. Mezey E, Kiss Z. Vasoactive intestinal peptide-containing neu- rons in the para ventricular nucleus may participate in regulating prolactin secretion. Proc Natl Acad Sci USA 1985;82:245-7.
92. Said SI, Porter Jc. Vasoactive intestinal polypeptide in rat hy- pophyseal portal blood. Life Sci 1979;24:227-30.
93. Samson WK, Bianchi R, Mogg RJ, Rivier J, Vale W, Melin P.
Oxytocin mediates the hypothalamic action of vasoactive in- testinal peptide to stimulate prolactin secretion. Endocrinology 1989;124:812-9.
94. Cohen H, Guillaumot P, Sabbagh I, Bertrand J. A new hypo- prolactinemic rat strain: luteinizing hormone, follicle-stimulat- ing hormone, testosterone and corticosterone levels in males and effects of two anesthetics. BioI Reprod 1983;28:122-7.
95. Coindet J, Chouvet G, Mouret J. Effect of lesions the supra- chiasmatic nuclei on paradoxical sleep and slow-wave sleep cir- cadian rhythms in the rat. Neurosci Lett 1975;1:243-7.
96. Piepenbrock N, Valatx JL, Malquarti V, Jouvet M. Effects of hypothalamic para ventricular lesion on sleep in rats. Neurosci Lett 1985;62:151-6.
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