Increase of prolactin mRNA in the rat hypothalamus after intracerebroventricular injection of VIP or PACAP

Vasoactive intestinal peptide (VIP), the structurally homologous pituitary adenylate cyclase-activating peptide (PACAP) and the pituitary hormone, prolactin (PRL) enhance rapid eye movement sleep (REMS). VIP and PACAP are both inducers of PRL gene expression and release in the pituitary gland. Little is known about PRL regulation in the brain although it is hypothesized that the REMS-promoting activity of i.c.v. administered VIP may be mediated via the activation of cerebral PRL. To test whether VIP or PACAP in fact increase intracerebral mRNA, the peptides (VIP: 30 or 300 pmol; PACAP: 220 pmol) were injected i.c.v. into rats at dark onset. 1 h later, cDNA was synthesized from purified hypothalamic mRNA. Standardized amounts were analysed for PRL using the polymerase chain reaction followed by Southern blotting and hybridization. Compared with β-actin mRNA levels, both VIP and PACAP increased PRL mRNA levels in a dose-dependent fashion though VIP was more effective on a molar basis. The previously reported alternatively spliced PRL mRNA (lacking exon 4) was not detected. The data support the hypothesis that the REMS-promoting activity of central VIP and PACAP might be mediated by cerebral PRL.     

Secretogranin I (chromogranin B) mRNA accumulation is hormonally regulated in GH3B6 rat pituitary tumor cells

Secretogranin I (SgI; chromogranin B) belongs to a class of acidic tyrosine-sulfated secretory proteins believed to play a role in the secretory process of endocrine cells. Our aim here was to compare the levels of SgI mRNA to that of prolactin (PRL) and growth hormone (GH), using rat pituitary cell lines. As far as the constitutive expression is concerned, we found a positive correlation between SgI mRNA and PRL mRNA levels. However, the neuropeptide TRH (50 nM) inhibited the accumulation of SgI mRNA in GH3B6 cells whereas, as expected, it induced a rapid and sustained increase in PRL mRNA accumulation. By contrast, 17β-estradiol (1 nM) stimulated the accumulation of both SgI and PRL mRNAs, with the same EC₅₀ (18–59 pM). Reciprocally, treatment with dexamethasone (100 nM) reduced the level of SgI and PRL mRNAs to 23% and 29% of control, respectively, but led to a 2.1-fold increase in the GH mRNA level. Altogether, the present work shows that SgI gene expression is subject to multiple hormonal regulations and occasionally parallels the regulation of the PRL gene but never that of the GH gene, under the conditions tested.     

Effect of pindolol on the prolactin response tod-denfluramine

We studied the effect of the 5-HT_1A receptor antagonist, pindolol, on the prolactin (PRL) response to the 5-HT releasing agent,d-fenfluramine (d-FEN), in ten healthy male volunteers. Pindolol pretreatment lowered baseline PRL levels but, when this effect was taken into account, did not significantly attenuate the PRL response tod-FEN. Within the limitations that attend the use of pindolol as a 5-HT_1A receptor antagonist, the data suggest that although 5-HT_1A receptors may play a role in the tonic release of PRL, they are not involved in the release of PRL produced byd-FEN. We propose that the PRL response tod-FEN may involve selective activation of postsynaptic 5-HT₂ receptors.     

Neonatal exposure to estradiol prevents the expression of ovarian hormone-induced luteinizing hormone and prolactin surges in adulthood but not antecedent changes in neuropeptide Y or adrenergic transmitter activity: Implications for sexual differentiation of gonadotropin secretion

Sex differences in adult patterns of mating behavior and gonadotropin secretion in rats are determined in part by the presence or absence of gonadal steroids during a perinatal critical period. For example, male rats and female rats exposed neonatally to androgen do not exhibit LH surge patterns when treated appropriately with ovarian hormones in adulthood, and there is evidence that this may be due to a failure of ovarian hormones to activate the hypothalamic neuronal systems that stimulate LH secretion in such animals. Because considerable evidence suggests that estradiol formed centrally from testosterone is responsible for the permanent defeminization of mating behavior and gonadotropin secretion, the present studies compared normal females with normal males and with females treated neonatally with estradiol on the ability of ovarian hormones to induce several important neurochemical changes antecedent to the LH surge, including changes in neuropeptide Y (NPY) and LH-releasing hormone (LHRH) concentrations in the median eminence, as well as changes in turnover rates for catecholamine transmitters in the medial basal hypothalamus and medial preoptic area. Normal ovariectomized female rats responded to sequential treatment with estradiol followed by progesterone with afternoon LH and prolactin (PRL) surges, and with sequential accumulation followed by decline in concentrations of LHRH and NPY in the median eminence prior to the LH surge. In addition, administration of progesterone increased the turnover rates of norepinephrine (NE) and epinephrine (EPI) in the arcuate-median eminence region of normal females. Gonadectomized male rats receiving the same ovarian hormone treatment failed to exhibit LH or PRL surges and displayed none of the changes in neurotransmitter turnover or peptide concentrations characteristically seen in the normal female. Unexpectedly however, when females that were treated with estradiol benzoate on days 1–3 postpartum were ovariectomized and treated with ovarian hormones in adulthood, they showed the same accumulation/decline in median eminence NPY concentrations and the same activation of NE and EPI turnover in the arcuate-median eminence region as normal females, even though they showed no LH or PRL surges or changes in median eminence LHRH concentrations. These results suggest that estradiol may not mediate all of the defeminizing actions of androgen exerted during the early neonatal period, and particularly those actions that result in a lack of responsiveness in central noradrenergic, adrenergic and NPY systems in adulthood. However, an action of neonatal estradiol may result in uncoupling of the LHRH neurosecretory system from normal excitatory neurochemical influences.     

Depriving neonatal rats of milk from early lactation has long-term consequences on mammotrope development

The sudden appearance of prolactin-releasing cells during the early postnatal period of the rat is initiated by a small milk-borne peptide. Depriving newborn rats of this early milk factor severely retards mammotrope differentiation during the neonatal period. In the present work, we extend our study of early milk deprivation to the adult. To this end, newborn litters were crossfostered onto mothers that had given birth the same day or one week earlier in order to deprive pups in the latter group of early milk. At 5, 15, and 30 d of age, rats deprived of such milk had decreased percentages of mammotropes (as measured by reverse hemolytic plaque assay, RHPA) when compared to nondeprived animals (P<0.05). By 45 d, the percentage of mammotropes was similar for the two crossfostered groups (P>0.1) and this persisted through d 60. Subsequently, we assessed the secretory capacity of mammotropes from 60-d old rats to secretagogues and found that early milk deprivation had no effect on basal prolactin release (P>0.1), but that it augmented hormone secretion evoked by thyrotropin-releasing hormone (TRH, 100 nM; P<0.01). The inhibitory response to dopamine (DA; 1 μM) and the stimulatory response to angiotensin II (AGII; 100 nM) were not altered by early milk deprivation (P>0.1). Taken together, these results demonstrate that factors in milk from early lactation are required for normal mammotrope differentiation, and that the delay induced by early milk deprivation leads to altered secretory function of mammotropes in adult animals.     

Neuroendocrine aspects of the serotonergic hypothesis of depression

This review examines the role of serotonin (5-HT) in depression. Dysfunction of serotonergic neurons has been implicated as one of the causes of endogenous depression. Since serotonergic neurons innervate the hypothalamus and these neurons send collaterals to several other brain areas, it is possible that hypothalamic sites which control hormone secretion receive the same serotonergic afferents that innervate other limbic areas in the brain. Several investigators have devised neuroendocrine challenge tests measuring the effect of 5-HT agonists on plasma cortisol and prolactin in depressed patients. These tests help to identify dysfunctional 5-HT neurons, and are a "window into the brain." The secretion of cortisol and prolactin is increased predominantly by 5-HT1 receptors. However, changes in 5-HT2 receptors have also been implicated in depression. Results from our laboratory and by others suggest that brain serotonergic neurons stimulate renin and vasopressin secretion by activation of 5-HT2 receptors. Therefore, the renin and vasopressin response to 5-HT agonists should be included in neuroendocrine tests of serotonergic function in affective disorders. Since antidepressants produce a decrease in the density of 5-HT2 receptors, renin and vasopressin could be used to evaluate the antidepressant potential of new drugs.     

Influence of shock-induced fighting and social factors on pituitary-adrenal activity, prolactin and catecholamine synthesizing enzymes in rats

The present experiment investigated changes in pituitary-adrenal activity, prolactin and catecholamine synthesizing enzymes in rats exposed to electric shocks in pairs or individually, in comparison to animals receiving no shock and tested in pairs or alone. Pairs of rats repeatedly exposed to electric shocks displayed a lower activation of the pituitary-adrenal system but a stronger activation of the sympathetic-adrenal medullary system than rats shocked individually. There was no differential release of prolactin according to the social setting in which shock occurred. Social factors by themselves influenced plasma corticosterone levels but not plasma levels of ACTH and prolactin nor catecholamine synthesis. The results are discussed in relation to the postulated beneficial effects of fighting on physiological activation produced by electric shock.     

大鼠肝细胞泌乳素受体的研究

本文以~(125)I-oPRL为放射催标记配体,利用受体放射分析法,对哺乳期大鼠肝细胞泌乳素受体进行了研究。结果表明。大鼠肝细胞泌乳素受体与泌乳素的结合具有高度特异性和可饱和性,而且受反应时间和pH值大小的影响;这种结合并非简单的双分子反应,大鼠肝细胞泌乳素受体很可能存在两种亲和力高低不同的结合位点(Kd_1=3.20×10~(10)M,Kd_2=1.26×10~(-8)M)或负协同调节。本研究为将来深入开展泌乳素对肝脏机能调节机制的探讨打下了基础。     

Regional changes in monoamine metabolism in the aging constant estrous rat

Studies were undertaken to determine levels of monoamines and their metabolites in brain regions in young (3–4 months) normally cycling and old (25–26 month) constant estrous female rats. Dopamine (DA) concentrations were reduced in old rats in the median eminence (ME), medial basal hypothalamus (MBH), preoptic area-anterior hypothalamus (POA-AH) and the striatum. Similarly, concentrations of dihydroxyphenylacetic acid (DOPAC), the major acid metabolite of DA, were reduced significantly in all 4 regions. In the ME, a strong positive correlation was observed between DA and DOPAC concentrations in both young and old rats. Concentrations of norepinephrine (NE) were reduced in old rats in the MBH and POA-AH but not in the ME or striatum. Concentrations of serotonin (5HT) and its major metabolite, 5-hydroxyindoleacetic acid (5HIAA) were generally unchanged with age in all of the regions examined. These studies indicate the age-related regional alterations in DA and 5HT metabolism can be monitored by methods which quantitate monoamines and their metabolites.     

Face cooling-induced reduction of plasma prolactin response to exercise as part of an integrated response to thermal stress

Summary This study was designed to verify if the decrease in blood prolactin (PRL) induced by selective face cooling during exercise could be part of a response to specific body thermal stress. Five healthy trained male cyclists presenting a significant plasma PRL elevation to exercise were, on three occasions and at weekly interval, submitted to a submaximal exercise (approx. 65% ) on ergocycle with and without selective face cooling. In absence of face cooling a first trial served to establish reference values for workload, heart rate and plasma PRL levels, the latter increasing markedly (450% of resting values) in these conditions. On a second trial but with workload maintained at reference values (222±9 W), a significant bradycardia was observed with face cooling; furthermore, plasma PRL response to exercise was significantly reduced (to 31% of original response). On a third trial with face cooling, workload had to be significantly augmented (242±10 W) to maintain heart rate at reference level (78%HR _max); in addition, plasma PRL response to exercise was almost unchanged compared to the reference-value level. The absence of a significant face cooling-induced decrease in sympathetic tonus, as evaluated through peripheral plasma catecholamines response, does not indicate a role for the autonomic nervous system in the face cooling-induced reduction of both heart rate and PRL responses during exercise. Assay of circulating peripheral beta-endorphins could indicate that the face cooling-induced PRL blunted response does not necessarily involve an opioid mediation. It was concluded that decreased plasma PRL levels could be associated to bradycardia, hyposudation and peripheral vaso-constriction to constitute an integrated response to face cooling during thermal stress. This study was supported by grants from Natural Sciences and Engineering Research Council of Canada and from Régie de la Sécurité dans les Sports du Québec