Showing papers on "Prolactin published in 1994"

Mammary gland factor (MGF) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response

Abstract: Milk protein gene expression in mammary epithelial cells is regulated by the action of the lactogenic hormones insulin, glucocorticoids and prolactin. The mammary gland factor, MGF, has been shown to be a central mediator in the lactogenic hormone response. The DNA binding activity of MGF is hormonally regulated and essential for beta-casein promoter activity. We have used Red A Sepharose- and sequence-specific DNA affinity chromatography to purify MGF from mammary gland tissue of lactating sheep. Proteins of 84 and 92 kDa were obtained, proteolytically digested and the resulting peptides separated by reverse phase high pressure liquid chromatography. The 84 and 92 kDa proteins yielded very similar peptide patterns. The amino acid sequence of two peptides was determined. The sequence information was used to derive oligonucleotide probes. A cDNA library from the mRNA of mammary gland tissue of lactating sheep was screened and a molecular clone encoding MGF was isolated. MGF consists of 734 amino acids and has sequence homology with the 113 (Stat113) and 91 kDa (Stat91) components of ISGF3, transcription factors which are signal transducers of IFN-alpha/beta and IFN-gamma. Two species of MGF mRNA of 6.5 and 4.5 kb were detected in mammary gland tissue of lactating sheep. Lower mRNA expression was found in ovary, thymus, spleen, kidney, lung, muscle and the adrenal gland. MGF cDNA was incorporated into a eukaryotic expression vector and cotransfected with a vector encoding the long form of the prolactin receptor into COS cells. A strong MGF-specific bandshift was obtained with nuclear extracts of COS cells induced with prolactin. Treatment of activated MGF with a tyrosine-specific protein phosphatase resulted in the loss of DNA binding activity. Prolactin-dependent transactivation of a beta-casein promoter-luciferase reporter gene construct was observed in transfected cells.

Photoperiodically-induced cycles in the secretion of prolactin in hypothalamo-pituitary disconnected rams: evidence for translation of the melatonin signal in the pituitary gland.

Abstract: Long term changes in the secretion of prolactin were monitored in groups of hypothalamo-pituitary disconnected rams (HPD rams, n = 8) and control rams (HPD sham-operated and unoperated, n = 8) while exposed to an artificial lighting regimen of alternating 16-weekly periods of long days (16L:8D) and short days (8L:16D) for 72 weeks, and during a treatment with subcutaneous constant-release implants of melatonin under long days. The HPD rams showed all the clinical characteristics of complete pituitary disconnection (diabetes insipidus, gonadal regression and slight obesity), and were unresponsive to a range of provocation tests (exposure to a barking sheep dog, cannulation of the jugular vein, injection of serotonin and NMDA) which caused acute changes in the blood plasma concentrations of prolactin in the controls. Nevertheless, there was a clearly defined cycle in the blood concentrations of prolactin in the HPD rams related to the imposed lighting regimen with values 10-fold higher under long days compared to short days (HPD mean +/- SEM: 90.1 +/- 24.7 vs 9.4 +/- 2.0 micrograms/l, long vs short day respectively, P < 0.001). The temporal pattern was very similar to that observed in the controls, although the concentrations of prolactin were higher in the HPD rams and more variable (control mean +/- SEM: 55.6 +/- 3.6 vs 3.0 +/- 0.5 micrograms/l, long vs short day, P < 0.001). There was a corresponding cycle in the growth and moulting of the wool in the HPD rams consistent with a biological response to the photoperiodically-induced changes in the secretion of prolactin. The diurnal rhythm in the blood concentrations of prolactin was absent in the HPD rams, but there was a normal rhythm in the secretion of melatonin. The treatment of the animals with constant-release implants of melatonin under long days caused a marked decrease in the blood concentrations of prolactin in both the HPD and control rams. The overall conclusion is that the endogenously generated daily melatonin signal which encodes daylength acts directly in the pituitary gland to mediate the effects of photo-period on the secretion of prolactin. The photo-period transduction pathway thus by-passes the hypothalamus.

Activation of JAK2 tyrosine kinase by prolactin receptors in Nb2 cells and mouse mammary gland explants

Abstract: One of the earliest cellular responses to prolactin (PRL) binding in Nb2 cells, a rat pre-T lymphoma cell line, is an increase in tyrosine phosphorylation of cellular proteins. In this work, immunologic techniques have been used to demonstrate that in Nb2 cells and in mouse mammary gland explants, JAK2, a non-receptor tyrosine kinase, is activated following stimulation with PRL. PRL stimulated tyrosine phosphorylation of JAK2 at times as early as 30 sec and concentrations of PRL as low as 0.5 ng/ml (2.5 pM) in Nb2 cells and 100 ng/ml (5 nM) in mammary gland explants. When JAK2 was immunoprecipitated from solubilized Nb2 cells or mammary gland explants and incubated with [gamma-32P]ATP, 32P was incorporated into a protein migrating with an apparent molecular weight appropriate for JAK2 only when cells had been incubated with PRL, indicating that JAK2 tyrosine kinase activity is exquisitely sensitive to PRL. In Nb2 cells, JAK2 was found to associate with PRL receptor irrespective of whether or not the cells had been incubated with PRL. These results provide strong evidence that JAK2 is constitutively associated with the PRL receptor and that it is activated and tyrosine phosphorylated upon PRL binding to the PRL receptor. These results are consistent with JAK2 serving as an early, perhaps initial, signaling molecule for PRL.

The protein tyrosine kinase P59fyn is associated with prolactin (PRL) receptor and is activated by PRL stimulation of T-lymphocytes.

Abstract: The clonal expansion of antigen-stimulated T-lymphocytes during an immune response is mediated by several lymphokines. Strong evidence now exists that the neuroendocrine hormone PRL is necessary, but not sufficient, for T-cell proliferation. Little is known, however, of the signal transduction mechanisms of the PRL receptor (PRLR) within T-cells. We demonstrate here that PRL stimulation of the T-cell line Nb2 induced the concentration- and time-dependent activation of the protein tyrosine kinase p59fyn, but not of four other src family protein tyrosine kinases. Activation of fyn was also observed in Concanavalin-A-primed peripheral blood lymphocytes stimulated with PRL and in Nb2 cells incubated with anti-PRLR antibodies. The activation of fyn by PRL stimulation correlated with Nb2 cell proliferation. Immunoblot analysis of anti-fyn and anti-PRLR immune complexes revealed an association between each PRLR isoform and p59fyn. These studies demonstrate for the first time an association between the PRLR and a...

Decreased Expression of the Two D2 Dopamine Receptor Isoforms in Bromocriptine-Resistant Prolactinomas

Abstract: Bromocriptine or other dopamine agonists are usually effective for the treatment of prolactin-secreting adenomas. Five to 18% of prolactinomas, however, do not respond to such therapy. We have shown previously that such resistance to bromocriptine correlates with reduced binding to the D2 receptor subtype of dopamine, the major PRL inhibiting factor. In the present work, we demonstrated that reduced binding actually corresponds to decreased expression of the gene coding for the D2 receptor in the pituitary from bromocriptine-resistant patients, as shown by 4-fold lower levels of the corresponding mRNAs compared to those coding for actin. The existence of two D2 receptor isoforms, D2S and D2L generated by alternative splicing, has been described in several tissues, including the pituitary. Both are negatively coupled to adenylyl cyclase and inhibit prolactin secretion, but, in addition, the shortest one (D2S) is more efficiently coupled to phospholipase C. Consequently, we also investigated whether expression of a particular D2 receptor isoform was preferentially affected in resistant adenomas. The proportion of messengers corresponding to the short receptor isoform (D2S) was lower in resistant compared to responsive adenomas: D2S/D2L = 0.74 ± 0.08 and 1.00 ± 0.07, respectively. In parallel, much lower levels of D2 receptor mRNAs were found in growth hormone-secreting adenomas, with a D2S/D2L ratio comparable to those of both normal human pituitary and bromocriptine-sensitive prolactinomas (1.05 ± 0.11). Thus, resistance to bromocriptine therapy seems to involve defects in D2 dopamine receptor expression and possibly in posttranscriptional splicing.

Physiological Mechanisms Underlying Lactational Amenorrhea

Abstract: Breastfeeding delays the resumption of normal ovarian cycles by disrupting the pattern of pulsatile release of GnRH from the hypothalamus and hence LH from the pituitary The plasma concentrations of FSH during lactation are sufficient to induce follicle growth, but the inadequate pulsatile LH signal results in a reduced estradiol production by these follicles When follicle growth and estradiol secretion does increase to normal, the suckling stimulus prevents the generation of a normal preovulatory LH surge and follicles either fail to rupture, or become atretic or cystic Only when the suckling stimulus declines sufficiently to allow generation of a normal preovulatory LH surge to occur will ovulation take place with the formation of a corpus luteum of variable normality Thus suckling delays the resumption of normal ovarian cyclicity by disrupting but not totally inhibiting, the normal pattern of release of GnRH by the hypothalamus The mechanism of suckling-induced disruption of GnRH release remains unknown It does not appear to involve prolactin, dopamine or opiates although a combination of these factors might be involved Prolactin is the major hormone responsible for milk production and is present in sufficient quantities in almost all women to allow the establishment of normal lactation Oxytocin is essential for milk let down and is susceptible to inhibition of release by stress The successful initiation of lactation which would lead to the potential of utilizing breastfeeding as contraceptive may require more attention to be paid to the establishment of non-stress release of oxytocin

Hypothesis for mammary tumorigenesis in Sprague‐Dawley rats exposed to certain triazine herbicides

Abstract: The symmetrical triazine herbicides have been used for the preemergence control of broadleaf weeds for nearly three decades. Recently, certain members of this class, primarily the chlorotriazines (substituted in the 2 position), have been shown to evoke an increased incidence of mammary tumors in female Sprague‐Dawley rats. This response was noted when these chemicals were administered in the diet for 2 yr, and most often at dietary feeding levels at or above the maximum tolerated dose (MTD). At levels exceeding the MTD the health of these animals was compromised, as manifested by toxicity‐related reduced survival that was not associated with the occurrence of mammary tumors. Mammary tumors in rats frequently occur as a result of the influence of endogenous estradiol and prolactin. Those hormones, as well as progesterone, growth‐stimulating, luteinizing, and follicle‐stimulating hormones, were measured after 24 mo of dietary administration of the chlorotriazine, simazine. The plasma hormone pattern seen i...

Effect of prolactin on the prostate

Abstract: We propose that: 1. Prolactin is a trophic hormone required for normal development and growth of prostate as well as other tissues. 2. Citrate production, the major function of prostate, is directly regulated by prolactin. 3. The mechanisms of prolactin regulation of citrate production by prostate epithelial cells include a. Regulation of the pmAAT gene, which results in an increase in the biosynthesis of mAAT and, ultimately, an increase in citrate synthesis (the prolactin regulation of gene transcription is mediated via PKC). b. Inhibition of citrate oxidation, possibly via zinc inhibition of m-aconitase. c. Stimulation of aspartate transport, possibly via regulation of the biosynthesis of the high-affinity aspartate transporter. 4. These relationships apply to normal human prostate, and might have important implications in the pathogenesis of prostate neoplasms. 5. The regulation of prostate citrate production is the reproductive function of prolactin in males.

Effects of the Menstrual Cycle on Dependent Variables in Mood Disorder Research

Abstract: The purpose of this article is to review the literature on the effects of the menstrual cycle on dependent variables in mood disorder research to inform investigators which physiological measures are likely to be significantly affected by menstrual cycle fluctuations and precisely how they might be affected. The following variables are discussed: prolactin; growth hormone; the hypothalamic-pituitary-thyroid axis (including thyrotropin, triiodothyronine, and thyroxine); the hypothalamic-pituitary-adrenal axis (cortisol, corticotropin, and beta-endorphin); melatonin; sleep; body temperature; and neurotransmitter activity (serotonergic and adrenergic systems). Body temperature and plasma and urinary norepinephrine vary predictably over the menstrual cycle. Prolactin and beta-endorphin may have peaks in the periovulatory phase, whereas serotonin levels in platelet-poor plasma may reach a nadir at that time. Triiodothyronine, thyroxine, cortisol, and melatonin do not appear to vary systematically over the course of the menstrual cycle, whereas the data for growth hormone, thyrotropin, corticotropin, and sleep are inconclusive.

Prolactin-producing pituitary adenoma in a male-to-female transsexual patient with protracted estrogen administration. A morphologic study.

Abstract: Pituitary adenoma developed in a 33-year-old male-to-female transsexual patient who was given estrogen, starting at 16 years of age; the pituitary adenoma was surgically removed and studied by light microscopy, immunocytochemistry, and in situ hybridization. The adenoma cells were immunoreactive for prolactin, and exhibited a strong signal for prolactin and estrogen receptor messenger RNAs and a weak signal for dopamine receptor messenger RNA. The question of whether the development of an adenoma was incidental or was the direct effect of estrogen or whether it was mediated via other mechanisms, such as activation of growth factors or oncogenes or inhibition of tumor-suppressing genes or other genetic abnormalities, remained unresolved. The present case, which, to our knowledge, is the first to describe structural findings of a pituitary adenoma in a transsexual patient who was given estrogen, reinforces the view that protracted stimulation may play a role in the genesis of endocrine tumors.

The 24-Hour Profiles of Cortisol, Prolactin, and Growth Hormone Secretion in Mania

Abstract: Objective: To characterize sleep and the 24-hour profiles of cortisol, prolactin (PRL), and growth hormone (GH) secretion in mania. Methods: Blood was sampled at 15-minute intervals, and sleep was polygraphically recorded in eight unmedicated male patients with pure mania and the results compared with those from a group of 14 healthy age-matched controls. The circadian, sleep-related, and pulsatile hormonal variations were quantitatively characterized using specially designed computer algorithms. Results: The manic state was associated with alterations of corticotropic activity and circadian rhythmicity partially overlapping those previously observed in acute endogenous depression, consisting of an elevation of nocturnal cortisol levels and an early timing of the nadir of the circadian variation. Sleep onset was delayed and the sleep period was reduced. A trend for short rapid eye movement latencies was apparent in the adult patients. Both the amount and the temporal organization of PRL and GH secretion were normal. Conclusion: The manic state seems to be characterized by similar but less severe neuroendocrine and circadian abnormalities, compared with major depression.

Evidence that growth hormone stimulates milk synthesis by direct action on the mammary gland and that prolactin exerts effects on milk secretion by maintenance of mammary deoxyribonucleic acid content and tight junction status.

Abstract: Both PRL and GH play a role in maintaining lactation in the rat, although GH can only maintain pup weight gain at around 50% of the control value, whereas PRL can maintain weight gain close to 90% in the absence of GH. In this study we examined the effects of PRL and GH deficiency (using bromocriptine and an antiserum to rat GH) on milk yield and composition in lactating rats. Treatment with bromocriptine to suppress PRL secretion for 48 h led to a 57% decrease in milk yield with a concomitant decrease in milk protein and lactose yields, but no decrease in fat output. This led to the production of milk with a lower lactose concentration but increased concentrations of protein and particularly fat (increased 100%), which suggests that GH serves an auxiliary role by maintaining an energy-rich milk for the neonate when PRL secretion is reduced. This decrease in milk synthesis was accompanied by decreases in total mammary DNA content and increased milk sodium concentrations. The latter indicates the opening of tight junctions between mammary epithelial cells, which normally occurs during dedifferentiation and involution of the mammary gland. This suggests that PRL maintains milk synthesis at least in part by inhibiting epithelial cell loss and maintaining cellular differentiation. A deficiency in GH, by contrast, caused only a small decrease (24%) in milk yield and had no effect on the major constituents of milk or on milk sodium concentrations or total mammary DNA content. When animals were made deficient in both PRL and GH, however, there was a further marked decrease (88%) in milk volume along with the yields of all major milk constituents, confirming our previous findings that PRL and GH are the major regulators of milk synthesis. Recent studies have indicated that GH exerts direct effects on mammary gland growth, but its actions on milk secretion have been proposed to be mediated indirectly via insulin-like growth factor-I (IGF-I). We, therefore, inhibited lactation by inducing PRL and GH deficiency for 48 h and then attempted to reinitiate it by administering GH either systemically or by local oil-based implants into the mammary gland. Oil-based GH implants were as effective in stimulating milk secretion in the treated (but not contralateral, control) gland as was systemic GH treatment. Thus, GH does act directly on the mammary gland to stimulate milk synthesis, although this does not rule out the possibility that GH acts by stimulating local production of IGF-I.(ABSTRACT TRUNCATED AT 400 WORDS)

Pituitary and adrenal hormone responses to pharmacological, physical, and psychological stimulation in habitual smokers and nonsmokers.

Abstract: Hormone responses to injection of corticotropin-releasing hormone following bicycle ergometry and psychological stress were studied in ten habitual smokers and ten nonsmokers. Compared to injection of saline, significant increases were found in adrenocorticotropin, prolactin, growth hormone, total serum cortisol, and salivary cortisol under all three stimulations except for salivary cortisol under ergometry. Furthermore, the smokers showed significant elevations of all five hormones investigated following the smoking of two cigarettes of the subject's preferred brand. Comparisons of hormone responses between smokers and nonsmokers revealed a general trend towards stronger responses in nonsmokers. However, due to the small number of subjects investigated and considerable variation in the individual hormone responses these differences reached statistical significance only for growth hormone responses following ergometry and salivary cortisol responses after psychological stress. In addition, the circadian rhythm of salivary cortisol was measured on two occasions between 9 a.m. and 9 p.m. in the subject's natural environment. The typical circadian pattern of decreasing cortisol levels was observed, with no significant differences between smokers and nonsmokers. We conclude that chronic nicotine consumption may lead to lower responses of multiple hormones not only to nicotine but to a variety of stimuli, and that these alterations do not necessarily affect unstimulated circadian profiles of free cortisol.

Neuroendocrine and Reproductive Consequences of Overexpression of Growth Hormone in Transgenic Mice

Abstract: Availability of recombinant growth hormone (GH) and development of long-acting formulations of this material will undoubtedly lead to widespread use of GH in animal industry and in medicine. GH can act, directly or indirectly, on multiple targets, but its influence on the reproductive system and on the hormonal control of reproduction is poorly understood. Overexpression of GH genes in transgenic animals provides a unique opportunity to study the effects of long-term GH excess. Transgenic mice overexpressing bovine, ovine, or rat GH (hormones with actions closely resembling, if not identical to, those of endogenous [mouse] GH), exhibit enhancement of growth, increased adult body size, and reduced life-span as well as a number of endocrine and reproductive abnormalities. Ectopic overexpression of bovine GH (bGH) driven by metallothionein or phosphoenolpyruvate carboxykinase promoters is associated with altered activity of hypothalamic neurons which produce somatostatin, loss of adenohypophyseal GH releasing hormone (GHRH) receptors, and suppression of endogenous (mouse) GH release. Elevation of plasma levels of GH (primarily bGH) and insulin-like growth factor (IGF-I) in these transgenic mice leads to increases in the number of hepatic GH and prolactin (PRL) receptors, in the serum levels of GH-binding protein (GHBP), in the percent of GHBP complexed with GH, and in the circulating insulin levels. In addition, plasma adrenocorticotropic hormone (ACTH) and corticosterone levels are elevated. Plasma levels of luteinizing hormone (LH), as well as its synthesis and release, are not consistently affected, but follicle-stimulating hormone (FSH) levels are suppressed, apparently due to pre- and post-translational effects. Pituitary lactotrophs exhibit characteristics of chronic enhancement of secretory activity, and plasma PRL levels are elevated. Prolactin responses to mating or to pharmacological blockade of dopamine synthesis are abnormal. Reproductive life span and efficiency are reduced in both sexes, with the severity and frequency of reproductive deficits being related to plasma bGH levels. Most transgenic females expressing high levels of bGH are sterile due to luteal failure. Overexpression of human GH which, in the mouse, interacts with both GH and PRL receptors leads to additional endocrine and reproductive abnormalities including stimulation of LH beta mRNA levels and LH secretion, loss of responsiveness to testosterone feedback, overstimulation of mammary glands, enhanced mammary tumorigenesis, and hypertrophy of accessory reproductive glands in males.

Prolactin receptor mRNA localization in the hypothalamus by in situ hybridization.

Abstract: Prolactin receptors may mediate the action of prolactin in the brain to influence behavior and neuroendocrine secretions. We recently demonstrated prolactin receptor gene expression in the anterior and medial basal hypothalamus and not in the cortex by the reverse transcription-polymerase chain reaction. In this paper, we localize the prolactin receptor gene expression to individual cells with in situ hybridization. Several steps in the in situ hybridization method were modified to increase sensitivity by using (i) probes complementary to the coding sequence of the extracellular binding domain common to both long and short prolactin receptor, (ii) more stringent hybridization and wash conditions to reduce background and (iii) higher specific activity, more complex and saturating amounts of probe. We detected prolactin receptor gene expression in cells of the periventricular area of the preoptic nucleus, medial preoptic nucleus, supraoptic nucleus, rostral arcuate nucleus and choroid plexus. Cortical brain tissue, which has been demonstrated previously by reverse-transcription polymerase chain reaction to be lacking in prolactin receptor mRNA, did not have any detectable signal for the receptor mRNA and was used as an indication of background levels of signal. The mean area of silver grains over labeled cells in periventricular area of the preoptic nucleus, medial preoptic nucleus, supraoptic nucleus, arcuate nucleus, lateral ventromedial nucleus was at least 10 times greater than the background in the cortex of the same brain section.

Inhibition of gonadotropin hormone-releasing hormone release by prolactin from GT1 neuronal cell lines through prolactin receptors.

Abstract: High levels of prolactin (PRL) are associated with inhibition of luteinizing hormone secretion in several mammalian species. We asked whether this phenomenon could be explained by a direct inhibitory action of PRL on hypothalamic gonadotropin hormone-releasing hormone (GnRH) neurons. The ability of PRL to suppress GnRH release and expression was tested in the highly differentiated GT1 GnRH cell lines. In static culture, nanomolar concentrations of either rat or mouse PRL inhibited the release of GnRH in a dose-dependent fashion. PRL treatment for 24 hr also decreased GnRH mRNA levels determined by Northern analysis. The cells were shown to express the PRL receptor gene, and the mRNAs for both the short and long forms were present by Northern and PCR analysis, although the short form was more abundant. In Western blots with monoclonal antibody against the rat liver PRL receptor, the short 42-kDa form of the receptor was observed. These results demonstrate that PRL inhibits GnRH release and possibly gene expression in GnRH neurons. This action appears to be mediated through prolactin receptors expressed by the cells.

Regulation of islet β-cell proliferation by prolactin in rat islets

Abstract: This study examined the effects of prolactin on β-cell proliferation in pancreatic islet of Langerhans. Insulin secretion and β-cell proliferation were significantly increased from neonatal rat islets cultured for 4 days in the presence of either 500 ng/ml ovine prolactin (oPRL) or rat prolactin (rPRL). These effects could be prevented by including anti-oPRL serum in the culture media. Although insulin secretion and β-cell proliferation were slightly higher during the first 24 h of exposure to rPRL, maximal response was observed after 4 days for insulin secretion and 6–10 days for β-cell proliferation. The initial mitogenic response of β-cell to rPRL occurred by the limited recruitment of nondividing β-cells into the cell cycle and by most daughter cells proceeding directly into additional cell division cycles. Subsequently, the maximal effect of rPRL on β-cell proliferation was maintained by a higher rate of recruitment of previously nondividing β-cells into cell cycle with only one fourth of the daughter cells continuing to divide. These observations are difficult to reconcile with the proposal that a limited pool of β-cells capable of undergoing cell division exists in islets. Instead, these observations suggest that individual β-cells are transiently re-entering the cell cycle and dividing infrequently in response to rPRL. In this case, the majority of the β-cells would not be expected to be in an irreversible G o phase. We also demonstrated that the effects of rPRL on β-cell proliferation occur at normal serum glucose concentrations and are affected by inhibitors of polyamine metabolism. Additional studies on the effects of rPRL on β-cells should provide important information on the regulation of β-cell proliferation during conditions of increased insulin demand.

Inhibition ofgonadotropin hormone-releasing hormonerelease by prolactin fromGT1neuronal cell lines through prolactin receptors

Abstract: Highlevels ofprolactin (PRL) areassociated withinhibition oflutelnizing hormone secretion inseveral mammalian species. Weasked whether this phenomenon could beexplained byadirect inhibitory action ofPRLonhypotha- lamic gonadotropin hormone-releasing hormone (GnRH) neu- rons. Theability ofPRL tosuppress GnRHrelease and expression wastested inthehighly differentiated GT1GnRH cell lines. Instatic culture, nmomolar concentrations ofeither ratormousePRLinhibited therelease ofGnRHinadose- dependent fashion. PRLtreatment for24hralso decreased GnRHmRNA levels determined byNorthern analysis. The cells wereshowntoexpress thePRLreceptor gene, andthe mRNAsforboththeshort andlongforms werepresent by Northern andPCRanalysis, although theshort formwasmore abundant. InWestern blots withmonoclonal antibody against theratliver PRLreceptor, theshort 42-kDaformofthe receptor wasobserved. Theseresults demonstrate that PRL inhibits GnRHrelease andpossibly geneexpression inGnRH neurons. Thisaction appears tobemediated through prolactin receptors expressed bythecells. During normal physiological states associated withelevated prolactin (PRL), luteinizing hormone (LH)levels arelow- ered-e.g., during pregnancy, pseudopregnancy, postpar- tum,andlactation (1,2).Inwomenelevated PRLlevels resulting fromananterior pituitary tumororthetherapeutic useofdopamine antagonists result inamenorrhea (1,2).

Seasonal and Fasting-Related Changes in Circulating Gonadal Steroids and Prolactin in King Penguins, Aptenodytes patagonicus

Abstract: Temporal correlations between reproductive endocrinology and the breeding and molt cycle of the king penguin were studied at the Crozet Islands, in the southern Indian Ocean. This species is unique in having a long cycle (14-15 mo), mainly due to a prolonged fledging period (11 mo), which includes the austral winter. Plasma gonadal steroids and prolactin were at their minimum levels during the prebreeding molt. However, circulating testosterone (males) and estradiol and progesterone (females) were already elevated at the time of arrival at the colony to breed, and the levels peaked during copulation. After laying plasma steroids decreased but remained above basal levels during the following months. Prolactin was low during the sexual phase of the reproductive cycle of both males and females. It reached high plasma concentrations in incubating birds and remained elevated during the whole fledging period. Possible roles for sustained high prolactin levels in winter and spring, which involve the care of the ...

The Brown Norway Rat as a Model of Male Reproductive Aging: Evidence for Both Primary and Secondary Testicular Failure

Abstract: In man, aging is associated with both primary and secondary testicular dysfunction. In contrast, most studies in male rat models of aging have demonstrated only secondary testicular failure. We previously reported that testes from aging male F344 rats secrete excessive progesterone (P), which may suppress gonadotropin secretion and confound aging studies. To determine whether the male Brown Norway (BN) rat is a more suitable aging model, trunk blood was collected from intact (sham-operated) and orchidectomized young (3 mo), middle-aged (13 mo), old (23 mo), and senescent (28-30 mo) animals. Testosterone (T), estradiol (E2), P, prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured by RIA. In intact rats, T levels declined with aging, while LH was unchanged, and FSH increased progressively with aging. In contrast to F344 rats, no age-related increases in P or E2 occurred, nor did PRL or other steroid hormones increase. In the absence of testicular feedback (orchidectomized rats), FSH and LH declined progressively with aging. These findings suggest that, as in men, aging male BN rats manifest both primary and secondary testicular failure, and do not exhibit decreased gonadotropin levels secondary to excessive steroid or PRL secretion. Therefore, the BN rat appears to be the best available rat model for studies of male reproductive aging.

Normal structural dopamine type 2 receptor gene in prolactin-secreting and other pituitary tumors.

Abstract: Dopamine, acting via its specific receptor (DRD2) in the anterior pituitary, tonically inhibits pituitary prolactin secretion and lactotroph proliferation. In addition, dopamine agonist therapy for pituitary prolactinomas results in reduction of prolactin secretion and tumor regression. These observations lead to the speculation that functional dopamine uncoupling may release lactotrophs from the inhibitory effects of dopamine and contribute to the development of prolactin (PRL)-secreting pituitary tumors. We hypothesized that such an uncoupling may occur by inactivating mutation(s) of the DRD2. To test our hypothesis, we examined 79 pituitary tumors, mostly prolactinomas and mixed GH/PRL-secreting, for mutations in the coding exons of the DRD2 gene. We used the polymerase chain reaction and analyzed the fragments for migration abnormalities on denaturing gradient gel electrophoresis, complemented by direct DNA sequencing. No mutations were demonstrated, and all migration abnormalities detected by denatur...