leptin and Hyperprolactinemia

Anovulatory infertility affects a large proportion of reproductive-aged women. Major improvements in successful clinical treatment of this prevalent disorder in women's health have been made possible because of biomedical research employing nonhuman primates. Experiments on female rhesus monkeys were the first to demonstrate that the key hypothalamic neurotransmitter, gonadotropin-releasing hormone, involved in stimulating pituitary gonadotropin synthesis, storage, and release was bioactive only when released in approximately hourly bursts. This breakthrough in understanding gonadotropin regulation enabled identification of hypogonadotropic, apparently normogonadotropic, and hypergonadotropic forms of anovulatory infertility, and development of appropriate stimulatory or inhibitory gonadotropin therapies. Treatments to overcome anovulatory infertility represent one of the major advances in clinical reproductive endocrinology during the last 25 yr. The future promise of nonhuman primate models for human ovulatory dysfunction, however, may be based on an increased understanding of molecular and physiological mechanisms responsible for fetal programming of adult metabolic and reproductive defects and for obesity-related, hyperinsulinemic impairment of oocyte development.

Topics: Animals; Anovulation; Disease Models, Animal; Female; Gonadotropin-Releasing Hormone; Humans; Hyperprolactinemia; Hypothalamus; Infertility, Female; Leptin; Ovarian Diseases; Primates; Stress, Physiological; Time Factors

An established fact in the polycystic ovarian syndrome (POS) is an abnormal ovarian steroidogenesis. Though this suggest an intrinsic ovarian defect, the syndrome could also be influenced by factors outside the ovaries. Although of unknown etiology, the POS is one of the most frequent endocrine disorders in the gynecologic practice. The disorder is characterized by ultrasound findings of enlarged polycystic ovaries, hyperandrogenism, menstrual disorders, obesity and including the appearance of infertility. There are a series of mechanisms involved in the extraovarian androgen increase in patients with POS. Among these mechanisms are implicated those of central and peripheral origin, genetic factors and adrenocortical dysfunction. In the same way, the alterations produced could imply genetic, molecular biological, biochemical, physiological and endocrinological factors. Sometimes all these factors could interact at the same time. The high serum androgen level could stop the pituitary gonadotropin production, either as a direct mechanism or as a result of its peripheral conversion. The increased androgens also explain the manifestations of clinical acne, hirsutism, and the detention in follicular ovarian maturation. All these manifestations are related with the menstrual disorders, anovulation, and infertility that these patients develop. The characteristics of the extraovarian POS include the 17-hydroxyprogesterone elevation in response to the ACTH test and the dexamethasone suppression of adrenal androgens. It is possible to improve the ovarian function in some patients with POS. This could be achieved with clomiphene citrate associated with glucocorticoids to induce ovulation.

Topics: 11-beta-Hydroxysteroid Dehydrogenases; 17-alpha-Hydroxyprogesterone; 3-Hydroxysteroid Dehydrogenases; Adrenal Cortex; Adrenal Hyperplasia, Congenital; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Adult; Androgens; Catecholamines; Clomiphene; Corticotropin-Releasing Hormone; Cortisone; Dexamethasone; Female; Glucocorticoids; Gonadal Steroid Hormones; Humans; Hydroxysteroid Dehydrogenases; Hyperinsulinism; Hyperprolactinemia; Hypothalamo-Hypophyseal System; Infant, Newborn; Infertility, Female; Insulin Resistance; Leptin; Mineralocorticoids; Obesity; Ovary; Ovulation Induction; Pituitary-Adrenal System; Polycystic Ovary Syndrome; Pseudopregnancy; Steroid 11-beta-Hydroxylase; Steroid 17-alpha-Hydroxylase; Steroids; Sterol Esterase; Stress, Psychological

Hormones such as prolactin and leptin have recently been recognized as potent platelet aggregation co-activators, and have therefore been postulated as an additional risk factor for both arterial and venous thrombosis. Clinical situations exist that are known to be associated with higher leptin and/or prolactin levels (obesity, pregnancy, prolactinomas and anti-psychotic therapy respectively) and increased venous thrombosis or atherosclerosis risk. Therefore, we compared the impact of both hormones on platelet activation in vitro and in vivo. First, we investigated platelet aggregation and P-selectin expression after stimulation with 1,000 mU/l prolactin or 100 ng/ml leptin in five healthy volunteers in vitro. Prolactin revealed significant higher levels of P-selectin expression and platelet aggregation than leptin in all subjects. We also compared the correlation of prolactin and leptin values with the P-selection expression on platelets. Previously, we detected a significant correlation between prolactin values and ADP-stimulated P-selectin expression on platelets in pregnant women, patients with pituitary tumours, and patients on anti-psychotic therapy. In contrast, leptin did not correlate with P-selectin expression in all subject groups investigated. However, leptin correlated with body mass index in the subjects investigated. Our data indicate that prolactin has a stronger effect on platelet activation as leptin in vitro and in vivo. Moreover, our data suggest that the stronger effect of prolactin on ADP-stimulated platelet aggregation, compared to leptin, depends on higher stimulation of CD62p expression by prolactin.

Topics: Antipsychotic Agents; Blood Platelets; Female; Humans; Hyperprolactinemia; Leptin; P-Selectin; Pituitary Neoplasms; Platelet Activation; Platelet Aggregation; Pregnancy; Prolactin; Prolactinoma; Reference Values; Statistics, Nonparametric

It has recently been shown that increased body weight is associated with prolactinomas and that weight loss occurs with normalization of prolactin levels. On the other hand, decreased dopaminergic tone in humans is well correlated with obesity. The objective of this study was to correlate changes in prolactin levels with leptin and body mass index (BMI) in patients with prolactinomas treated with the long-acting dopamine agonist bromocriptine (BC).. Eleven female and twelve male patients, aged 36.7+/-2.6 years with BMI in males of 30.4+/-1.7 kg/m(2) and in females of 24.4+/-1.2 kg/m(2), were evaluated after 1 and 6 months and 11 patients were further evaluated after 2 years of BC therapy. Plasma prolactin is presented as the mean of four samples taken daily. Serum leptin was determined in the pooled serum from three samples taken at 15-min intervals at 0800 h after an overnight fast. Multivariate linear regression and repeated measures analysis of covariance were used.. In males, pretreatment prolactin levels were 71 362+/-29 912 mU/l while leptin levels were 14.9+/-1.8 microg/l. In females, pretreatment prolactin levels were 11 395+/-5839 mU/l and leptin levels were 16.7+/-2.5 microg/l. The sexual dimorphism of serum leptin levels at initial presentation was preserved after adjusting for BMI and prolactin-induced hypogonadism. After 1 month of therapy, prolactin levels significantly decreased (males: 17 618+/-8736 mU/l, females: 3686+/-2231; P<0.05), BMI did not change (males: 30.2+/-1.7 kg/m(2), females: 24.1+/-1.2 kg/m(2); P>0.05), while serum leptin levels decreased (males: 12.5+/-1.5 microg/l, females: 13.6+/-2.1 microg/l; P<0.05). After 6 months of treatment, prolactin further decreased (males: 3456+/-2101 mU/l, females: 677+/-360 mU/l; P<0.05) as did BMI (males: 28.6+/-1.6 kg/m(2), females 23.1+/-1.0 kg/m(2); P<0.05). The difference was more pronounced in male patients. Leptin levels were 12.8+/-2.8 microg/l in males and 12.9+/-1.8 microg/l in females (P<0.05). After 2 years of BC treatment, prolactin levels were near normal (males: 665+/-439 mU/l, females 447+/-130 mU/l; P<0.05) and BMI remained 26.5+/-1.9 kg/m(2) for males and 23.6+/-0.8 kg/m(2) for females (P<0.05). Leptin levels were 9.5+/-2.2 microg/l in males and 18.7+/-3.1 microg/l in females (P<0.05). There was a gradual increase in the gender difference in serum leptin levels over time. Changes in serum leptin levels significantly correlated with changes in BMI (r=0.844, P<0.001) but did not correlate with changes in plasma prolactin levels after 1 month (r=0.166), 6 months (r=0.313) and 2 years (r=0.234, P>0.05).. The long-acting dopamine agonist BC, by increasing dopaminergic tone, may influence body weight and likely body composition by mechanisms in addition to reducing hyperprolactinemia in patients with prolactinomas.

Topics: Adolescent; Adult; Basal Metabolism; Body Weight; Bromocriptine; Dopamine; Female; Hormone Antagonists; Humans; Hyperprolactinemia; Leptin; Male; Middle Aged; Obesity; Pituitary Neoplasms; Prolactin; Prolactinoma

Knowledge of chronic kidney disease (CKD) with pubertal disorders (PD) in adolescent boys is limited as few studies have explored this disorder. This study aimed to identify the usefulness of assessing hormonal parameters in male adolescents with CKD and their correlation with PD in a 12-month follow-up period.. A prospective cohort study was conducted among male adolescents with CKD (stages IV and V). Data regarding the age at puberty onset were collected from the patients' clinical records and through interview. The patients were followed up for 12 months during their pubertal development. At the beginning, routine hormonal profile tests were performed to examine the patients' thyroid profile, prolactin levels, luteinizing hormone, follicle-stimulating hormone, testosterone, leptin, and receptor leptin. The hormonal profiles of patients with and without PD were compared. Comparisons between the groups were performed using the Student t-test and Fisher's exact tests. Logistic regression analysis was also performed.. Data of 64 patients (26/64 with PD) were analyzed. The median age was 15 years and the median time for CKD evolution was 11 months. No differences between groups were noted in the general or biochemical characteristics of the patients. The hormonal parameters, prolactin levels were higher and the free leptin and free thyroxine levels were lower in patients with PD. Leptin receptor levels of >0.90 ng/mL (risk ratio [RR], 8.6; P = 0.004) and hyperprolactinemia (RR, 21.3; P = 0.049) were the risk factors for PD.. Leptin receptor levels of >0.90 ng/mL and hyperprolactinemia are associated with the development of PD in male adolescents with CKD.

Topics: Adolescent; Humans; Hyperprolactinemia; Leptin; Male; Prolactin; Prospective Studies; Puberty; Receptors, Leptin; Renal Insufficiency, Chronic

We evaluated maternal flaxseed oil intake during lactation on body composition, lipid profile, glucose homeostasis and adipose tissue inflammation in male and female progeny at adulthood. Lactating rats were divided into the following: control 7% soybean oil (C), hyper 19% soybean oil (HS) and hyper 17% flaxseed oil+2% soybean oil (HF). Weaned pups received a standard diet. Offspring were killed in PN180. Male HF presented higher visceral adipose tissue (VAT) and triacylglycerol, and female HF showed insulin resistance. Both male and female HF had hyperleptinemia, and only male HF had hyperprolactinemia. In VAT, male HF presented lower PPAR-γ expressions and higher TNF-α, IL-6, IL-1β and IL-10 expressions; in subcutaneous adipose tissue (SAT), they presented lower PPAR-γ and TNF-α expressions. Female HF presented higher leptin, as well as lower adiponectin, TNF-α, IL-6 and IL-1β expressions in VAT and lower TNF-α in SAT. Flaxseed oil during lactation leads to gender-specific effects with more adiposity and dyslipidemia in male and insulin resistance in female. Higher prolactin and inflammatory cytokines in male could play a role in these gender differences. We suggest that the use of flaxseed oil during lactation increases metabolic syndrome risk in the adult progeny.

Topics: Adiposity; Animals; Biomarkers; Diet, High-Fat; Dyslipidemias; Female; Hyperprolactinemia; Inflammation Mediators; Insulin Resistance; Intra-Abdominal Fat; Lactation; Leptin; Linseed Oil; Male; Maternal Nutritional Physiological Phenomena; PPAR gamma; Random Allocation; Rats, Wistar; Sex Factors; Subcutaneous Fat

The effects of hyperprolactinemia on metabolic parameters are not clear and a few data evaluating adiponectin levels in prolactinoma and idiopathic hyperprolactinemia exist. The aim of this study was to evaluate the effects of hyperprolactinemia on body weight, insulin resistance, beta cell function, and leptin and adiponectin levels in premenopausal women with hyperprolactinemia. Forty premenopausal women with prolactinoma or idiopathic hyperprolactinemia were compared to 41 age-matched healthy premenopausal women with regard to body weight, body mass index, waist and hip circumferences, waist to hip ratio, fasting plasma glucose, insulin levels, insulin resistance measured by homeostasis model assessment (HOMA)-insulin resistance index, beta cell function measured by HOMA-β index, leptin and adiponectin levels. Plasma insulin levels and HOMA indexes (both insulin resistance and beta indexes) were significantly higher in hyperprolactinemic women. The other parameters were similar between both groups. There was a positive correlation between prolactin levels and fasting plasma glucose in hyperprolactinemic women. The results of this study showed that high prolactin levels may be associated with hyperinsulinemia and insulin resistance in premenopausal women. This effect seems to be independent of body weight, leptin and adiponectin levels. High prolactin levels may directly stimulate insulin secretion from pancreas and directly cause hepatic and whole-body insulin resistance.

Topics: Adiponectin; Adolescent; Adult; Blood Glucose; Body Composition; Body Weight; Female; Humans; Hyperprolactinemia; Insulin; Insulin Resistance; Leptin; Middle Aged; Premenopause; Waist-Hip Ratio

Leptin is a key mediator in the maintenance of neuroendocrine homeostasis. The aim of this study was to determine the changes in serum leptin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), nitric oxide (NO) levels in patients with hyperprolactinemia. The study consists of 16 consecutive patients with high prolactin (PRL) levels (group I) and a control group of 11 normoprolactinemic patients (group II). Pituitary tumor tissues of patients in groups I and II were analyzed for immunohistochemical (IHC) expression of prolactin and leptin. Group I has significantly higher levels of leptin than group II (P < 0.001). There is a strong correlation between PRL and leptin concentrations in group I. However, there were no statistically significant differences for NO, TNF-alpha, IL-6 between the two groups. IHC staining showed that there was strong immunoreactivity for leptin protein in PRL-secreting pituitary adenomas. Double immunostaining of adenoma tissues with PRL and leptin showed that the adenoma cells expressed both. These findings together are suggestive that leptin co-secretion from a prolactinoma may be the cause of increased serum leptin concentration, independently from the peripheral action of prolactin.

Topics: Adult; Female; Humans; Hyperprolactinemia; Immunohistochemistry; Interleukin-6; Leptin; Male; Middle Aged; Nitric Oxide; Pituitary Neoplasms; Prolactin; Tumor Necrosis Factor-alpha

Leptin, the obese (Ob) gene product, is an adipocyte-derived satiety factor that is involved in the regulation of food intake and body weight. Leptin signals nutritional status to several other physiological systems and modulates their function. As PRL is involved in energy and lipid metabolism, this study was undertaken to investigate the role of PRL on in vivo regulation of leptin serum concentration and Ob messenger RNA expression in white adipose tissue in rats. It was found that increased serum PRL levels, obtained by pituitary graft or exogenous injected ovine PRL (oPRL, 5 mg/kg), significantly stimulate serum leptin concentration. A significant increase (P < 0.01) in serum leptin concentration was present in hyperprolactinemic animals (4.7+/-0.4 microg/liter) in comparison to controls (1.2+/-0.1 microg/liter and 1.09+/-0.09 microg/liter of intact sham operated and ovariectomized rats, respectively). Similar results were obtained in oPRL-treated animals where leptin levels were 5.4+/-0.1 microg/liter vs. 1.1+/-0.1 microg/liter and 0.8+/-0.08 microg/liter of intact sham operated rats and ovariectomized, respectively (P < 0.001). This stimulatory effect of PRL on serum leptin levels was significantly reduced by food deprivation (P < 0.01) where serum leptin levels were 12.5+/-0.65 microg/liter in grafted animals vs. 3.2+/-0.36 microg/liter of grafted animals subjected to 48 h of food deprivation. Moreover, in vivo, PRL was able to induce leptin messenger RNA levels in several areas of rat white adipose tissue. The data demonstrate that PRL acts on the adipose tissue increasing leptin synthesis and secretion, suggesting a new role for this lactogenic hormone in the regulation of food intake.

Topics: Adipose Tissue; Animals; Female; Gene Expression; Hyperprolactinemia; Kidney; Leptin; Ovariectomy; Pituitary Gland; Prolactin; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transplantation, Heterotopic