Mary Lage

Serum leptin levels in women throughout pregnancy and the postpartum period and in women suffering spontaneous abortion

In pregnancy, important changes occur in the body weight of the mother, caused by sodium and water retention and by an increase in body fat tissue, but the mechanisms that regulate maternal and foetal changes in fat mass are poorly understood. Leptin is a hormone produced by adipocytes in order to regulate food intake and energy expenditure at the hypothalamic level in man. In order to verify whether leptin participates in the changes in body composition during pregnancy and postpartum, 630 healthy women were studied at specific time periods and leptin and auxological parameters were determined.

Ghrelin levels are suppressed and show a blunted response to oral glucose in women with polycystic ovary syndrome.

OBJECTIVE Abnormal ghrelin regulation may influence the development of obesity-associated conditions including polycystic ovary syndrome (PCOS). Our aim was to compare ghrelin regulation between PCOS cases and controls. DESIGN We compared serum ghrelin (total) levels, fasting and 30-min post-oral (75 g) glucose load, between 50 PCOS cases and 28 female controls, including 22 body mass index (BMI)/fat mass-matched pairs. All subjects were of UK British/Irish origin. METHODS Measurements included serum ghrelin (RIA technique (LINCO Research, St Charles MO, USA)), fat mass, serum testosterone, fasting serum insulin and plasma glucose levels. Insulin sensitivity was calculated as the homeostasis model assessment of insulin resistance (HOMA2 IR). RESULTS Fasting serum ghrelin levels were significantly lower in PCOS cases versus BMI/fat mass-matched controls (geometric mean (s.d. range), 1104 pg/ml (764-1595) vs 1756 pg/ml (1314-2347) respectively; P=2.3 x 10(-4)). Ghrelin suppression following oral glucose load was significantly blunted in PCOS cases versus BMI/fat mass-matched controls (geometric mean ghrelin suppression (s.d. range), 160 pg/ml (88-289) vs 424 pg/ml (220-818) respectively; P=2.0 x 10(-4)). Whole-group comparisons (50 PCOS cases versus 28 controls) adjusted for fat mass and age revealed similar results. In PCOS cases, there was a significant negative correlation between fasting serum ghrelin and HOMA2 IR (r(2)=-0.40, P=5.7 x 10(-3)). Following adjustment for HOMA2 IR, fat mass and age, comparisons between the whole groups of PCOS cases and controls revealed attenuated but significant differences in fasting serum ghrelin (P=1.3 x 10(-3)) and ghrelin suppression (P=1.8 x 10(-3)). CONCLUSIONS In women with PCOS, serum ghrelin levels are suppressed, showing a negative relationship with HOMA2 IR and a blunted response to oral glucose.

Evidence of free leptin in human seminal plasma

Leptin is an adipose tissue-secreted hormone that actively participates in the regulation of energy homeostasis. Besides this principal role, leptin has been implicated in a large variety of neuroendocrine, paracrine, and autocrine actions involved in the regulation of reproductive function in both experimental animals and humans. Although the participation of leptin in female reproduction is well established, any role in male reproductive function is at best tenuous. The aim of this study was to ascertain whether true leptin is present in human seminal fluid and the tissue of its production. Pooled human seminal plasma obtained from healthy donors showed by direct radioimmunoassay (RIA) the presence of radioimmunoassayable leptin. Serial dilutions of unextracted semen paralleled the RIA standard curve, also devoid of interference in the assay. To prove that this activity was true leptin, seminal plasma was subjected to size-exclusion chromatography, which showed that leptin immunoreactivity eluted with the same partition coefficient as cold leptin, 125I-leptin, and 125I-leptin preincubated with seminal plasma. The results demonstrate that true leptin was present in semen in a free form, i.e., without binding proteins. The presence of leptin charge variants in seminal plasma was assessed by anion-exchange chromatography, which showed two peaks of leptin inmunoreactivity, while 125I-leptin eluted as a single peak. Preincubation of 125I-leptin with seminal fluid converted the single peak into a double peak, indicating that components of the seminal fluid introduce a charge variation in leptin. Leptin levels in seminal plasma of 40 healthy men were 0.95±0.19 ng/mL while in 5 vasectomized men the levels were 0.92±0.25 ng/mL, suggesting that testicular tissues were not the source of seminal leptin. No correlation was observed between leptin concentrations in semen and the physical characteristics of semen samples or physical characteristics of spermatozoids, such as concentration, motility, vitality, or morphology. In conclusion it was unambiguously demonstrated that human leptin is present in seminal fluid, with at least two charge variants and no binding proteins, the most likely source being either seminal vesicles or prostate tissue. The role of seminal fluid leptin in the male reproductive function or sperm capacitation is at present unknown.

High serum leptin levels in children with type 1 diabetes mellitus : Contribution of age, BMI, pubertal development and metabolic status

Children with diabetes mellitus are prone to develop obesity and to experience a delay in onset of the pubertal process. In order to understand the role of leptin in these abnormalities, serum leptin levels were analysed in children with type 1 diabetes mellitus.

Hypopituitarism and Growth Hormone Deficiency in Adult Subjects after Traumatic Brain Injury: Who and When to Test

Traumatic brain injury (TBI) was traditionally considered an infrequent cause of hypopituitarism. However recent reports strongly suggest that TBI-mediated pituitary hormones deficiency may well be more frequent than previously thought. As the prevalence of hypopituitarism is not dependent on the severity of the trauma and considering the high number of TBI events in all industrialized countries a screening procedure for detecting hormone deficiencies in all TBI patients is not possible. In the present work a suggestion for screening a subgroup of TBI patients is discussed in order to increase the effectiveness of the whole procedure.

Testing Growth Hormone Deficiency in Adults

Growth hormone deficiency (GHD) in adults is a recognized syndrome which is defined biochemically within an appropriate clinical context. Clinically, patients investigated for GHD should include those with signs and symptoms of hypothalamic-pituitary disease, those who have received cranial irradiation or tumor treatment and those with traumatic brain injury or subarachnoid hemorrhage. Patients with three or more pituitary hormone deficiencies and an IGF-I below the reference range do not require provocative testing. The other patients need a provocative test of GH secretory reserve for the diagnosis of GHD. Insulin tolerance test is considered the diagnostic test of choice, however, the GH-releasing hormone (GHRH)+arginine, the GHRH+growth hormone-releasing peptide and the glucagon stimulation tests are well validated alternative tests in adults. Cutoffs differ across tests and results may be influenced by gender, age, body mass index, and the assay reference preparation.

cis-FFA do not alter membrane depolarization but block Ca2+ influx and GH secretion in KCl-stimulated somatotroph cells.: Suggestion for a direct cis-FFA perturbation of the Ca2+ channel opening

It has been reported that cis-unsaturated free fatty acids (cis-FFA) block intracellular Ca2+ rise in EGFR T17 and GH3 cells by perturbing the generation of Ins(1,4,5)P3. In the present work, it was found that cis-FFA did not alter potassium-induced cell depolarization in GH3 cells, while blocking Ca2+ rise and GH secretion. Interestingly enough, saturated or trans-unsaturated FFA exert the opposite actions, i.e., they block cell depolarization without altering Ca2+ rise and hormone secretion. As depolarization activates GH3 cells via direct opening of Ca2+ channels with no generation of intracellular mediators, these results suggest that cis-FFA act by a direct perturbation of the Ca2+ channel opening.

Role of leptin and ghrelin in the regulation of gonadal function

Gonadal development and function is sustained by the complex interaction of an array of regulatory signals that operate directly on the gonads and/or indirectly via modulation of gonadotropin secretion. During the last decade, different factors primarily involved in the control of food intake and energy balance have been demonstrated as putative modulators of different elements of the reproductive axis, including the gonads, thus helping to define the neuroendocrine basis for the link between body energy stores and fertility. These factors include not only the adipocyte-derived hormone leptin, which is indispensable for proper energy balance and reproduction, but also a number of neuropeptides and hormones of central and peripheral origin. In the latter, growing evidence strongly suggests the involvement of the stomach-secreted peptide ghrelin in the control of several aspects of gonadal function. Interestingly, leptin and ghrelin have been proposed as reciprocally related regulators of energy homeostasis; however, their potential interplay in the control of reproduction remains ill defined. This work will summarize the most salient findings concerning the potential roles of leptin and ghrelin in the functional control of the gonads. In addition, open issues regarding the reproductive facets of these metabolic signals will be highlighted. Overall, the authors propose that through complementary or antagonistic actions, leptin and ghrelin may jointly cooperate to modulate a wide set of reproductive functions, thereby contributing to the physiologic integration of energy balance and reproduction.