Showing papers on "Prolactin published in 2003"

Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin.

Abstract: Neurogenesis occurs in the olfactory system of the adult brain throughout life, in both invertebrates and vertebrates, but its physiological regulation is not understood. We show that the production of neuronal progenitors is stimulated in the forebrain subventricular zone of female mice during pregnancy and that this effect is mediated by the hormone prolactin. The progenitors then migrate to produce new olfactory interneurons, a process likely to be important for maternal behavior, because olfactory discrimination is critical for recognition and rearing of offspring. Neurogenesis occurs even in females that mate with sterile males. These findings imply that forebrain olfactory neurogenesis may contribute to adaptive behaviors in mating and pregnancy.

Sexual Differentiation, Pregnancy, Calorie Restriction, and Aging Affect the Adipocyte-Specific Secretory Protein Adiponectin

Abstract: Adiponectin or adipocyte complement-related protein of 30 kDa (Acrp30) is a circulating protein produced exclusively in adipocytes. Circulating Acrp30 levels have been associated with insulin sensitivity in adult mice and humans, yet the Acrp30 profile over the lifespan and its hormonal regulation in vivo have not been previously described. Hence, we set forth to determine whether hormonal and metabolic changes associated with sexual maturation, reproduction, aging, and calorie restriction affect Acrp30. In mice, Acrp30 levels increase during sexual maturation by 4-fold in males and 10-fold in females. Neonatal castration (CX) allows Acrp30 of adults to reach female levels. CX in adults does not lead to female Acrp30 levels unless glucocorticoid exposure is elevated simultaneously by implant. Ovariectomy of infant mice does not interfere with the pubertal rise of Acrp30. However, ovariectomy in adults increases Acrp30. Estrogen suppressed Acrp30 in mice and 3T3-L1 adipocytes. In parallel to changes in estrogen action, Acrp30 decreased in late gestation but increased in both calorie-restricted and old (anovulatory) mice. The reduction of Acrp30 in lactating dams is consistent with a suppressive effect of prolactin and a stimulating effect of bromocriptine. In summary, Acrp30 levels in serum are under complex hormonal control and may play a key role in determining systemic insulin sensitivity under the respective conditions.

The Role of Prolactin in Mammary Carcinoma

Abstract: The contribution of prolactin (PRL) to the pathogenesis and progression of human breast cancer at the cellular, transgenic, and epidemiological levels is increasingly appreciated. Acting at the endocrine and autocrine/paracrine levels, PRL functions to stimulate the growth and motility of human breast cancer cells. The actions of this ligand are mediated by at least six recognized PRL receptor isoforms found on, or secreted by, human breast epithelium. The PRL/PRL receptor complex associates with and activates several signaling networks that are shared with other members of the cytokine receptor superfamily. Coupled with the recently identified intranuclear function of PRL, these networks are integrated into the in vitro and in vivo actions induced by ligand. These findings indicate that antagonists of PRL/PRL receptor interaction or PRL receptor-associated signal transduction may be of considerable utility in the treatment of human breast cancer.

Prolactin induces ERα-positive and ERα-negative mammary cancer in transgenic mice

Abstract: The role of prolactin in human breast cancer has been controversial. However, it is now apparent that human mammary epithelial cells can synthesize prolactin endogenously, permitting autocrine/paracrine actions within the mammary gland that are independent of pituitary prolactin. To model this local mammary production of prolactin (PRL), we have generated mice that overexpress prolactin within mammary epithelial cells under the control of a hormonally nonresponsive promoter, neu-related lipocalin (NRL). In each of the two examined NRL-PRL transgenic mouse lineages, female virgin mice display mammary developmental abnormalities, mammary intraepithelial neoplasias, and invasive neoplasms. Prolactin increases proliferation in morphologically normal alveoli and ducts, as well as in lesions. The tumors are of varied histotype, but papillary adenocarcinomas and adenosquamous neoplasms predominate. Neoplasms can be separated into two populations: one is estrogen receptor alpha (ERα) positive (greater than 15% of the cells stain for ERα), and the other is ERα− (<3%). ERα expression does not correlate with tumor histotype, or proliferative or apoptotic indices. These studies provide a mouse model of hormonally dependent breast cancer, and, perhaps most strikingly, a model in which some neoplasms retain ERα, as occurs in the human disease.

Specificity of the neuroendocrine response to orgasm during sexual arousal in men

Abstract: We have demonstrated that sexual activity produces transient sympathoadrenal activation and a pronounced, longlasting increase in prolactin in men and women. However, by analyzing endocrine alterations at 10-min intervals, a precise assignment of these changes to the pre-, peri- and postorgasmic periods was not possible. Thus, the current study aimed to accurately differentiate the endocrine response to sexual arousal and orgasm in men using an automatic blood collection technique with 2-min sampling intervals. Blood was drawn continuously before, during and after orgasm over a total period of 40 min in 10 healthy subjects and were compared with samples obtained under a control condition. Sexual activity induced transient increases of plasma epinephrine and norepinephrine levels during orgasm with a rapid decline thereafter. In contrast, prolactin levels increased immediately after orgasm and remained elevated throughout the experiment. Although oxytocin was acutely increased after orgasm, these changes were not consistent and did not reach statistical significance. Vasopressin, LH, FSH and testosterone plasma concentrations remained unaltered during sexual arousal and orgasm. These data confirm that prolactin is secreted after orgasm and, compared with oxytocin, seems to represent a more reliable and sustained marker for orgasm in man. The results further reinforce a role for prolactin either as a neuroendocrine reproductive reflex or as a feedback mechanism modulating dopaminergic systems in the central nervous system that are responsible for appetitive behavior.

The maternal endocrine environment in the low-protein model of intra-uterine growth restriction.

Abstract: Many adult diseases, including type 2 diabetes, hypertension and cardiovascular disease, are related to low birth weight. The mechanistic basis of this relationship is not known. To investigate the role of fetal undernutrition, we used a rat model of maternal protein restriction in which dams were fed a diet containing 80 g protein/kg (v. 200 g/kg in the control group) throughout gestation and lactation. Offspring were born smaller than controls and in adulthood developed diabetes, hyperinsulinaemia and tissue insulin resistance. To determine possible mechanisms of fetal programming, circulating levels of several hormones were measured in maternal plasma at gestational days 14, 17 and 21 and fetal plasma at gestational day 21. Several differences were noted at day 14, when glucose concentrations in maternal and feto-placental blood were raised significantly (P=0.04 and P=0.0001 respectively); insulin levels in the low-protein (LP) dams were raised (P=0.04), prolactin levels were raised (P=0.047) and progesterone levels were reduced (P=0.02). Circulating 17beta-oestradiol in the LP dams was raised by 35 % over those of the controls from day 17 to day 21 (P=0.008). A significant decrease in maternal leptin levels (P=0.004) was observed at gestation on day 21. Neither oestradiol nor leptin levels were altered in the fetal circulation at day 21. Maternal and fetal corticosterone levels were comparable with control levels, suggesting that they do not initiate the programming effects in this model. Our present results suggest that maternal protein restriction imposes changes in maternal levels of glucose, insulin, prolactin, progesterone, oestradiol and leptin; these changes could influence the programming of eventual adult disease in the developing fetus.

TSH stimulates leptin secretion by a direct effect on adipocytes.

Abstract: Leptin is a circulating hormone secreted by adipose tissue which acts as a signal to the central nervous system where it regulates energy homeostasis and neuroendocrine processes. Although leptin modulates the secretion of several pituitary hormones, no information is available regarding a direct action of pituitary products on leptin release. However, it has been pointed out that leptin and TSH have a coordinated pulsatility in plasma. In order to test a direct action of TSH on in vitro leptin secretion, a systematic study of organ cultures of human omental adipose tissue was performed in samples obtained at surgery from 34 patients of both sexes during elective abdominal surgery. TSH powerfully stimulated leptin secretion by human adipose tissue in vitro. In contrast, prolactin, ACTH, FSH and LH were devoid of action. These results suggest that leptin and the thyroid axis maintain a complex and dual relationship and open the possibility that plasmatic changes in TSH may contribute to the regulation of leptin pulses.

Identification of tilapia ghrelin and its effects on growth hormone and prolactin release in the tilapia, Oreochromis mossambicus

Abstract: We have identified ghrelin and cDNA encoding precursor protein from the stomach of a euryhaline tilapia, Oreochromis mossambicus. The sequence of 20-amino acid tilapia ghrelin is GSSFLSPSQKPQNKVKSSRI. The third serine residue was modified by n-decanoic acid. The carboxyl-terminal end of the peptide possessed an amide structure. RT-PCR analysis revealed high levels of gene expression in the stomach and low levels in the brain, kidney and gill. Tilapia ghrelin stimulated growth hormone (GH) and prolactin (PRL) release from the organ-cultured tilapia pituitary at a dose of 10 nM. Thus, a novel regulatory mechanism of GH secretion by gastric ghrelin seems to be conserved in the tilapia. Stimulation of PRL release by homologous ghrelin has been reported in human, bullfrog and eel, and suggests the presence of growth hormone secretagogue receptor not only on somatotrophs but also on PRL cells of the tilapia pituitary.

Prolactin modulates the naive B cell repertoire

Abstract: Prolactin is a peptide hormone produced by the anterior pituitary gland that is critical in lactation. Prolactin can also be produced by lymphocytes, and both B and T cells express prolactin receptors. These findings have suggested that prolactin has immunomodulatory functions. Studies in spontaneously autoimmune hosts have demonstrated a role for prolactin in augmenting autoreactivity. We chose to analyze prolactin effects on anti-DNA B cells in nonspontaneously autoimmune female BALB/c mice transgenic for the heavy chain of an anti-DNA antibody. Treatment with prolactin for 4 weeks induced a lupus-like phenotype with an increased number of transgene-expressing B cells, elevated serum anti-DNA antibody titers, and glomerular immunoglobulin deposits. Prolactin caused a decrease in the population of transitional B cells and an increase in mature follicular and marginal zone B cells. The DNA-reactive B cells had a follicular cell phenotype. Anti-DNA hybridomas demonstrated that prolactin alters selection of the naive B cell repertoire. The expansion and activation of anti-DNA B cells in prolactin-treated R4A-γ2b BALB/c mice was dependent on the presence of CD4+ T cells. Finally, treatment with prolactin was unable to break tolerance in R4A-γ2b transgenic C57Bl/6 mice, suggesting that responsiveness of the immune system to prolactin is genetically determined.

Investigation of the transcriptional changes underlying functional defects in the mammary glands of prolactin receptor knockout mice.

Abstract: Knockout (KO) mice have been created that carry null mutations of genes encoding molecules essential for prolactin (PRL) release, PRL, the receptor for prolactin (PRLR), and various members of the receptor’s signaling pathway. This allowed an in vivo genetic analysis of the role of PRL in target organ function. In PRLKO and PRLRKO mice, mammary ductal side branching was absent, terminal end bud (TEB)-like structures persisted at the ductal termini well into maturity, and no alveolar buds formed along the ductal tree. Transplants of recombined mammary glands formed from stromal and epithelial elements with and without PRLR showed normal development, while supplementation of progesterone levels in PRLKO animals restored ductal side branching. During pregnancy, PRLR heterozygous animals initially showed normal ductal and alveolar development. However, alveolar development stalled during late pregnancy, preventing successful lactation. This defect could be rescued by the loss of a single allele of the suppressor of cytokine signaling (SOCS) 1 gene. Transplants of recombined glands containing PRLRKO epithelium and wild-type (WT) stroma formed alveolar buds during pregnancy but showed no lobuloalveolar development. Recombinations of WT epithelium and PRLRKO stroma showed normal development, demonstrating that a direct action of the lactogenic hormones is confined to the epithelium, to promote lobuloalveolar development. Transcript profiling of epithelial transplants expressing or not expressing PRLR was used during early pregnancy to investigate the transcriptional response to lactogens underlying this defect. Such profiling has identified a number of genes with well-characterized roles in mammary development, in addition to a number of novel transcripts.

Serum prolactin and TSH in an in vitro fertilization population: is there a link between fertilization and thyroid function?

Abstract: Purpose : Measurements of TSH and prolactin are generally included in the evaluation of female infertility, but their value in women coming to in vitro fertilization (IVF) has been questioned Methods : In this study, we sought to investigate whether prolactin or TSH, measured in 509 specimens collected prior to therapy, predicted outcome in a prospective study of couples undergoing IVF between 1994 and 2001 Results : TSH was higher in women whose fertility problem was attributed to a male factor, and prolactin was lower if the measurement was taken during menses TSH and prolactin were positively correlated (p < 00001) Neither TSH nor prolactin levels correlated with overall IVF outcome; however, TSH levels were significantly higher among women who produced oocytes that failed to be fertilized and this finding persisted after adjustment for several covariates, including sperm motility Among women who had a least one oocyte inseminated, the likelihood that they would have fewer than 50% of their eggs fertilized was significantly related to higher TSH levels in a multivariate model Conclusion : We conclude that TSH may predict poor fertilization in IVF and reflect the importance of thyroid hormones in oocyte physiology

Effects of deletion of the prolactin receptor on ovarian gene expression

Abstract: Prolactin (PRL) exerts pleiotropic physiological effects in various cells and tissues, and is mainly considered as a regulator of reproduction and cell growth. Null mutation of the PRL receptor (R) gene leads to female sterility due to a complete failure of embryo implantation. Pre-implantatory egg development, implantation and decidualization in the mouse appear to be dependent on ovarian rather than uterine PRLR expression, since progesterone replacement permits the rescue of normal implantation and early pregnancy. To better understand PRL receptor deficiency, we analyzed in detail ovarian and corpora lutea development of PRLR-/- females. The present study demonstrates that the ovulation rate is not different between PRLR+/+ and PRLR-/- mice. The corpus luteum is formed but an elevated level of apoptosis and extensive inhibition of angiogenesis occur during the luteal transition in the absence of prolactin signaling. These modifications lead to the decrease of LH receptor expression and consequently to a loss of the enzymatic cascades necessary to produce adequate levels of progesterone which are required for the maintenance of pregnancy.

Dysfunction of the hypothalamic-pituitary-glandular axes and relation to Child-Pugh classification in male patients with alcoholic and virus-related cirrhosis.

Abstract: ObjectiveTo investigate anterior pituitary function (adrenal, somatotropic, thyroid and gonadal axes, and prolactin) in relation to the Child-Pugh score in male patients with alcoholic and virus-related liver cirrhosis.MethodAnterior pituitary function was evaluated in 52 male cirrhotics (26 Child-P

Effects of acute prolactin manipulation on sexual drive and function in males.

Abstract: The neuroendocrine response to sexual activity in humans is characterized by a pronounced orgasm-dependent increase of plasma levels of prolactin. In contrast to the well-known inhibitory effects of chronic hyperprolactinemia on sexual drive and function, the impact of acute prolactin alterations on human sexual physiology is unknown. Therefore, this study was designed to investigate the effects of acute manipulation of plasma prolactin on sexual behavior. Ten healthy males participated in a single-blind, placebo-controlled, balanced cross-over design. Prolactin levels were pharmacologically increased to high levels (protirelin, 50 micro g i.v.) or reduced to low physiological concentrations (cabergoline, 0.5 mg p.o.). Sexual arousal and orgasm were then induced by an erotic film and masturbation. In addition to continuous neuroendocrine and cardiovascular recordings, the quality and intensity of the acute sexual drive, arousal, orgasm and refractory period were assessed by extensive psychometric measures. Administration of cabergoline decreased prolactin levels and significantly enhanced all parameters of sexual drive (P<0.05), function (P<0.01) and positive perception of the refractory period (P<0.01). Administration of protirelin increased prolactin concentrations and produced small, but not significant reductions of sexual parameters. The sexual effects observed from cabergoline were completely abrogated by coadministration of protirelin. Although different pharmacological sites of action of prolactin-altering drugs have to be considered, these data demonstrate that acute changes in prolactin plasma levels may be one factor modulating sexual drive and function. Therefore, besides a neuroendocrine reproductive reflex, a post-orgasmic prolactin increase may represent one factor modulating central nervous system centers controlling sexual drive and behavior. These findings may offer a new pharmacological approach for the treatment of sexual disorders.

Prostate Hyperplasia in a Transgenic Mouse with Prostate-Specific Expression of Prolactin

Abstract: Prolactin (PRL) is one of several polypeptide factors known to exert trophic effects on the prostate. We have previously reported a dramatic prostate enlargement with concurrent chronic hyperprolactinemia and elevated serum androgen levels in a PRL transgenic mouse (Mt-PRL) with ubiquitous expression of the transgene. To address the role of local PRL action in the prostate, a new transgenic mouse model (Pb-PRL) was generated using the prostate-specific rat probasin (Pb) minimal promoter to drive expression of the rat PRL gene. Pb-PRL transgenic males developed a significant enlargement of both the dorsolateral and ventral prostate lobes evident from 10 wk of age and increasing with age. Expression of the transgene was restricted to the prostate and detected from 4 wk of age. Low levels of transgenic rat PRL were detectable in the serum of adult Pb-PRL animals. Serum androgen levels were normal. The Pb-PRL prostate displayed significant stromal hyperplasia, ductal dilation, and focal areas of epithelial dysplasia. Quantitative analysis of prostatic tissue cellularity demonstrated a marked increase in the stromal to epithelial ratio in all lobes of Mt-PRL and Pb-PRL transgenic prostates compared with controls. Microdissections demonstrated an increased ductal morphogenesis in dorsolateral and ventral prostate lobes of Mt-PRL prostate vs. Pb-PRL and controls. In conclusion, this study indicates the ability of PRL to promote, directly or indirectly, ductal morphogenesis in the developing prostate and further to induce abnormal growth primarily of the stroma in the adult gland in a setting of normal androgen levels.

The role of C/EBPbeta in mammary gland development and breast cancer.

Abstract: The CCAAT/enhancer binding protein (C/EBP) family of bZIP transcription factors control the proliferation and differentiation of a variety of tissues. While C/EBPalpha and -delta are also expressed in the mammary gland, the multiple protein isoforms of C/EBPbeta appear to play a critical role in mammary gland development and breast cancer. Targeted deletion of all the C/EBPbeta isoforms results in a severe inhibition of lobuloalveolar development and a block to functional differentiation, as well as more subtle changes in ductal morphogenesis. The altered expression of a number of molecular markers, including the progesterone, estrogen, and prolactin receptors, the transporter proteins (NKCC1 and aquaporin 5), and several markers of skin differentiation (Sprr2A and keratin 6), suggests that germline deletion of C/EBPbeta results in an altered cell fate. Thus, C/EBPbeta appears to play a role in the specification of progenitor cell fate not only in the mammary gland, but also in a number of other tissues.

Are cadmium effects on plasma gonadotropins, prolactin, ACTH, GH and TSH levels, dose-dependent?

Abstract: It is well established that cadmium affects plasma levels of the pituitary hormones studied. However, whether the effects of the metal are dose dependent needs to be clarify. This work was designed to evaluate the possible changes in plasma levels of gonadotropins, prolactin, ACTH, GH and TSH after oral cadmium exposure in adult male rats. Plasma levels of these hormones were measured in adult male rats exposed to cadmium chloride (CdCl2) in the drinking water at the doses of 5, 10, 25, 50 or 100 ppm for one month. The lower dose of cadmium increased plasma prolactin levels and higher doses of the metal (25 or 50 ppm) decreased them. There was a continuous increase of plasma ACTH levels from the lower to 25 ppm dose of CdCl2 and decreased them after to basal values with the highest dose. Plasma GH levels were increased with the dose of cadmium of 10 ppm, although the doses of 5, 25 and 50 ppm decreased them. Plasma LH levels were only reduced with the dose of 50 ppm of CdCl2, whereas those of FSH increased. Plasma TSH levels were increased with the doses of 5, 25 and 100 ppm of CdCl2. Cadmium concentration increased in pituitary with the doses of 125, 50 and 100 ppm of CdCl2. These data suggest that cadmium differentially affects the secretory mechanisms of the pituitary hormones studied depending on the dose used. The effects of the metal on prolactin and ACTH are dose-dependent.

Prolactin regulation of estrogen receptor expression.

Abstract: The ability of the rat corpus luteum to respond to estrogen requires prolactin (PRL), which can stimulate the expression of the estrogen receptor (ER). This review will focus on the signaling mechanisms by which this occurs. Transcription of the genes encoding both ERα ( Esr1 ) and ERβ ( Esr2 ) is stimulated by PRL through the Jak2–Stat5 pathway and Stat5-response elements that are located in each of the Esr promoters. A single nucleotide difference between these two response elements is responsible for the observation that either Stat5a or Stat5b can stimulate Esr1 transcription, whereas only Stat5b can activate transcription of Esr2 . The tyrosine kinase Jak2 is required for PRL activation of Esr1 promoter activity; however, additional pathways are involved in PRL-induced Stat5b phosphorylation, nuclear translocation and DNA binding. In addition to the corpus luteum, PRL-induced ER expression might provide a mechanism for fine-tuning the responsiveness of other target tissues, such as the decidua and mammary gland, to these two hormones.

Local Insulin-Like Growth Factor-II Mediates Prolactin-Induced Mammary Gland Development

Abstract: Prolactin (PRL) is a major determinant of mammary epithelial cell proliferation during alveolar development in sexually mature and pregnant mice. To date, it has not been clear whether PRL effects these responses alone or by also invoking the action of autocrine/paracrine growth factors. In this study, we provide evidence that part of the effect of PRL on mammary gland growth is mediated by IGF-II. During sexual maturity and in early pregnancy, the level of IGF-II mRNA in the mammary gland was increased concurrent with increased PRL receptor expression. The level of IGF-II mRNA was reduced in mammary tissue from PRL receptor-/- mice during early pregnancy, and explants of mouse mammary gland and HC11 mammary epithelial cells both increased their expression of IGF-II after exposure to PRL in vitro. These findings coincided with the demonstration that IGF-II stimulated alveolar development in mammary glands in whole organ culture. PRL was most efficacious in stimulating IGF-II gene transcription from promoter 3 of the mouse IGF-II gene in vitro. Insight into the mechanism by which PRL induced IGF-II expression was provided by the fact that it was blocked by the Jak2 inhibitor AG490 and the MAPK inhibitor PD98059. Finally, induction of insulin receptor substrate (IRS)-1 in the mammary glands of PRL-treated mice and induction of IRS-1 and IRS-2 after treatment with PRL plus progesterone indicates that these molecules are induced by PRL as potential signaling intermediates downstream from IGF-I/insulin receptors. Together, these data demonstrate a role for IGF-II as a mediator of PRL action in the mouse mammary gland during ductal branching and alveolar development.

Immune and hormonal changes following intense military training.

Abstract: This study was designed to determine whether the immune and hormonal systems were affected by a 5-day military course following 3 weeks of combat training in a population of 26 male soldiers (mean age, 21 +/- 2 years). The combination of continuous heavy physical activity and sleep deprivation led to energy deficiency. At the beginning of the training program and immediately after the combat course, saliva samples were assayed for secretory immunoglobulin A and plasma samples were assayed for interleukin-6, dehydroepiandrosterone sulfate, prolactin, catecholamines, glucocorticoids, and testosterone. Secretory immunoglobulin A was lower and circulating interleukin-6 was increased by the end of the course, which was attributed to sympathoadrenergic stimulation. Dehydroepiandrosterone sulfate, prolactin, and testosterone levels fell significantly. These results suggest that prolonged and repeated exercise such as that encountered in a military training program induces immune impairment via a decrease in mucosal immunity and a release of interleukin-6 into the circulation. The impaired secretion of dehydroepiandrosterone sulfate and prolactin, two immunomodulatory hormones, was thought to be a response to the chronic stressors. Lowered testosterone reflects a general decrease in steroid synthesis as a consequence of the physical and psychological strain.

Prolactin expression and secretion by human breast glandular and adipose tissue explants.

Abstract: Prolactin (PRL) is a 23-kDa hormone produced by the pituitary and extrapituitary sites. The main target of PRL is the breast, where it affects cellular growth, differentiation, and milk production. Recent evidence suggests that locally produced PRL plays a role in breast tumorigenesis. Our objective was to examine PRL synthesis/release in different tissues of the human breast and determine the effect of ovarian steroids. Breast tissue, obtained from women undergoing mastectomy or breast reduction, was separated into glandular (nonmalignant) and adipose explants and incubated for 10 d. Conditioned media were analyzed for PRL by a bioassay. PRL release from glandular explants decreased by 60% from d 1-3, followed by a 4-fold increase on d 10. PRL release from adipose explants was unchanged from d 1-3 and increased more than 10-fold by d 10. PRL gene expression, determined by RT-PCR, was low on d 0 and markedly increased on d 10 in both types of explants. De novo synthesis of PRL was confirmed by metabolic labeling. Progesterone suppressed PRL release from glandular explants without affecting adipose explants. Estradiol did not alter PRL release from either tissue. In conclusion, the human breast produces and releases bioactive PRL, with a higher release rate by adipose than glandular tissue. The time-dependent rise in PRL release suggests removal from inhibitory control. Progesterone may be one of the factors that suppresses PRL production in the glandular compartment, whereas the factor(s) that regulate adipose PRL are unknown. These data suggest an autocrine/paracrine role for PRL in human glandular and adipose breast tissue.

Hyperprolactinemia in men: clinical and biochemical features and response to treatment.

Abstract: Hyperprolactinemia induces hypogonadism by inhibiting gonadotropin-releasing hormone pulsatile secretion and, consequently, follicle-stimulating hormone, luteinizing hormone, and testosterone pulsatility. This leads to spermatogenic arrest, impaired motility, and sperm quality and results in morphologic alterations of the testes similar to those observed in prepubertal testes. Men with hyperprolactinemia present more frequently with a macroadenoma than a microadenoma. Symptoms directly related to hypogonadism are prevalent. In men hypogonadism leads to impaired libido, erectile dysfunction, diminished ejaculate volume, and oligospermia. It is present in 16% of patients with erectile dysfunction and in approx 11% of men with oligospermia. Treatment with bromocriptine or cabergoline (CAB) is effective in men with prolactinomas, with a response that is in general comparable to treatment in women. Seminal fluid abnormalities rapidly improve with CAB treatment, while other dopaminergic compounds require longer periods of treatment. Moreover, to improve gonadal function in men, the integrity of the hypothalamic-pituitary-gonadal axis is necessary. New promising data indicate that a substantial proportion of patients with either micro- or macroprolactinoma do not present hyperprolactinemia after long-term withdrawal from CAB. Whether this corresponds to a definitive cure is still unknown, but treat-ment withdrawal should be attempted in patients achieving normalization of prolactin levels and disappearance of tumor mass to investigate this issue.

Effect of renal transplantation on sperm quality and sex hormone levels.

Abstract: OBJECTIVE To assess the effect of successful renal transplantation on semen variables, sexual function and sex hormone profiles in a clinical trial. PATIENTS AND METHODS Thirty patients on haemodialysis underwent renal transplantation; before and after surgery, their sperm density, motility and morphology were analysed, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin and testosterone levels measured and compared, and sexual function assessed using an abbreviated version of the International Index of Erectile Function (IIEF), with a successful outcome defined as a level of satisfaction of 4 or 5 on a 5-point scale. The paired t-test was used to assess the statistically significance of differences in all analyses. RESULTS Sperm motility improved significantly (P < 0.001) but there were no significant changes in morphology or density (P = 0.33 and 0.068, respectively). Testosterone levels increased and FSH, LH and prolactin decreased significantly (P < 0.05) after renal transplantation. The IIEF showed that of the 30 patients, 14 were impotent before surgery and only six remained so afterward (P < 0.05). CONCLUSION Although sperm morphology and density did not improve after renal transplantation, there were highly significant changes in sperm motility. Hormonal levels in patients on haemodialysis improved after transplantation and returned to nearly normal; sexual function was also significantly better. Further studies are needed to confirm these results.

Melatonin Modulates Secretion of Growth Hormone and Prolactin by Trout Pituitary Glands and Cells in Culture

Abstract: In Teleost fish, development, growth, and reproduction are influenced by the daily and seasonal variations of photoperiod and temperature. Early in vivo studies indicated the pineal gland mediates the effects of these external factors, most probably through the rhythmic production of melatonin. The present investigation was aimed at determining whether melatonin acts directly on the pituitary to control GH and prolactin (PRL) secretion in rainbow trout. We show that 2-[125I]-iodomelatonin, a melatonin analog, binds selectively to membrane preparations and tissue sections from trout pituitaries. The affinity was within the range of that found for the binding to brain microsomal preparations, but the number of binding sites was 20-fold less than in the brain. In culture, melatonin inhibited pituitary cAMP accumulation induced by forskolin, the adenyl cyclase stimulator. Forskolin also induced an increase in GH release, which was reduced in the presence of picomolar concentrations of melatonin. At higher con...

Lower cortisol and higher ACTH levels in individuals with autism.

Abstract: Blood concentrations of pituitary hormones adrenocorticotropin (ACTH), prolactin, growth hormone, and adrenal hormone-cortisol were measured in 36 autistic and 27 control individuals. Individuals with autism had significantly lower serum concentrations of cortisol (p < 10(-6)), and significantly higher concentrations of ACTH (p = 0.002) than control age- and sex-matched subjects. Also, prolactin concentrations in autistic patients with epilepsy were significantly higher when compared with normal subjects. The observed hormonal changes may indicate dysfunction of the hypothalamo-pituitary-adrenal axis in individuals with autism.