Diana Maas

Leptin: a significant indicator of total body fat but not of visceral fat and insulin insensitivity in African-American women.

The recently cloned adipose tissue hormone leptin has been proposed to be involved in the neuroendocrine regulation of adiposity and its metabolic sequelae. Visceral fat is known to predict reduced insulin sensitivity and associated adverse metabolic profiles. In this study, we report the first evaluation of the relationships between leptin levels and total body fat, visceral fat, and insulin sensitivity in a cohort of premenopausal African-American women. Thirty-four subjects were analyzed for total fat mass and visceral fat by dual-energy X-ray absorptiometry and computerized axial tomography, respectively. Insulin sensitivity (SI) was assessed using Bergmans minimal model. Results showed that fasting leptin levels strongly correlated with total body fat mass (r = 0.797, P < 0.001). Correlations of leptin with visceral fat (r = 0.54, P < 0.001) and SI (r = −0.419, P = 0.02) were dependent on total body fat. In conclusion, leptin levels reflect total body fat mass, and although visceral fat is known to predict reduced insulin sensitivity independently, leptin did not. Our data thus suggest that diverse mechanisms are responsible for the regulation of total body versus visceral fat distribution, with its metabolic and health risks.

Role of Hormones in the Pathogenesis and Management of Sarcopenia

There is growing evidence to indicate that age-related declines in growth hormone (GH), insulin-like growth factor (IGF)-1, and androgen and estrogen production play a role in the pathogenesis of sarcopenia (an age-related decline in muscle mass and quality). Although GH supplementation has been reported to increase lean body mass in elderly individuals, the high incidence of adverse effects combined with a very high cost has limited the applicability of this form of therapy. The assessment of an alternative approach to enhance the GH/IGF-1 axis in the elderly by using GH-releasing hormone and other secretagogues is currently under way and is showing some promise. Testosterone replacement therapy may increase muscle mass and strength and decrease body fat in hypogonadal elderly men. Long-term randomised, controlled trials are needed, however, to better define the risk-benefit ratio of this form of therapy before it can be recommended. Available data are currently insufficient to decide what role estrogen replacement therapy may play in the management of sarcopenia.Therefore, although the evidence linking age-related hormonal changes to the development of sarcopenia is rapidly growing, it is still too early to determine the clinical utility of hormonal supplementation in the management of sarcopenia.

Age-related changes in male gonadal function. Implications for therapy.

SummaryIn contrast with women, who experience a complete and abrupt cessation of ovarian function during the menopause, aging men largely maintain their testicular androgen production. Nevertheless, most cross-sectional studies indicate that there is a partial decrease in testosterone levels with aging, although this has not been confirmed by other studies. The disparity among studies stems from differences in study design, patient numbers, assay techniques and inclusion criteria. Proposed mechanisms for an age-associated decline in testosterone production include: (i) defects in the hypothalamic-pituitary-testicular axis; (ii) an increase in sex hormone binding globulin levels; (iii) environmental factors; (iv) medication use; and (v) chronic illness.The potential beneficial effects of testosterone replacement therapy in hypogonadal men include increased bone density, increased muscle strength, an improved feeling of well-being and an improved metabolic profile. These benefits need to be weighed against the potential risks of androgen therapy, such as erythrocytosis, sleep apnoea, and the stimulation of benign prostatic hypertrophy or an occult prostate malignancy. Consequently, androgen replacement should be used with caution in elderly men with hypogonadism until the results of well-controlled prospective studies are available.

Effect of Treatment Modality on the Hypothalamic–Pituitary Function of Patients Treated with Radiation Therapy for Pituitary Adenomas: Hypothalamic Dose and Endocrine Outcomes

Background: Both fractionated external beam radiotherapy and single fraction radiosurgery for pituitary adenomas are associated with the risk of hypothalamic–pituitary (HP) axis dysfunction. Objective: To analyze the effect of treatment modality (Linac, TomoTherapy, or gamma knife) on hypothalamic dose and correlate these with HP-axis deficits after radiotherapy. Methods: Radiation plans of patients treated post-operatively for pituitary adenomas using Linac-based 3D-conformal radiotherapy (CRT) (n = 11), TomoTherapy-based intensity modulated radiation therapy (IMRT) (n = 10), or gamma knife stereotactic radiosurgery (n = 12) were retrospectively reviewed. Dose to the hypothalamus was analyzed and post-radiotherapy hormone function including growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, prolactin, and gonadotropins (follicle stimulating hormone/luteinizing hormone) were assessed. Results: Post-radiation, 13 of 27 (48%) patients eligible for analysis developed at least one new hormone deficit, of which 8 of 11 (72%) occurred in the Linac group, 4 of 8 (50%) occurred in the TomoTherapy group, and 1 of 8 (12.5%) occurred in the gamma knife group. Compared with fractionated techniques, gamma knife showed improved hypothalamic sparing for DMax Hypo and V12Gy. For fractionated modalities, TomoTherapy showed improved dosimetric characteristics over Linac-based treatment with hypothalamic DMean (44.8 vs. 26.8 Gy p = 0.02), DMax (49.8 vs. 39.1 Gy p = 0.04), and V12Gy (100 vs. 76% p = 0.004). Conclusion: Maximal dosimetric avoidance of the hypothalamus was achieved using gamma knife-based radiosurgery followed by TomoTherapy-based IMRT, and Linac-based 3D conformal radiation therapy, respectively.

DYNAMICS OF PROLACTIN SECRETION FROM DIETHYLSTILBESTROL-INDUCED RAT PROLACTINOMA TISSUE IN VITRO

Abstract Experiments were performed to determine whether PRL secretion in the rat diethylstilbestrol (DES)-induced prolactinoma model is affected by the addition of thyrotropin-releasing hormone (TRH) and/or immunoneutralization of intrapituitary vasoactive intestinal polypeptide (VIP) in vitro. Male Fischer 344 rats were implanted with either a 10 mg DES or placebo pellet 30 days prior to obtaining the anterior pituitary glands for perifusion. The anterior pituitaries were quartered and used in three different perifusion experiments. In Experiment I, placebo-treated tissue channels were perifused for 2 baseline hr followed consecutively by a 30-min exposure to 1:100 nonimmune rabbit serum (NRS), a 30-min wash, and a final 30-min exposure to 10-5 M TRH. Additional placebo channels were run as above except 1:100 VIP antiserum (AVIP) was substituted for NRS and AVIP was added to the TRH. In Experiment II, the same perifusion protocol was used as in Experiment I, except DES-Induced tumor tissue was used instead of placebo tissue. Results from Experiment I and II reveal that AVIP significantly decreased PRL secretory rate in both DES and placebo groups. In the tumor group, both TRH alone and in the presence of AVIP significantly increased the PRL secretory rate. In Experiment III DES-Induced tumor tissue channels were perifused with a similar protocol, except the concentrations of NRS and AVIP were increased to 1:10. Both NRS and AVIP significantly decreased PRL secretory rate; however, AVIP had a significantly greater effect than NRS. In this experiment, 1:10 AVIP overcame the stimulatory effect of TRH. In conclusion, AVIP decreases and TRH increases, even in the presence of AVIP, PRL release in DES-induced prolactinoma tissue in vitro. Increasing the AVIP concentration 10-fold diminished the PRL-releasing action of TRH in the tumor tissue. These data suggest that PRL secretion is not autonomous in these prolactinomas and can be affected by exogenous TRH and partial immunoneutralization of endogenous VIP.

Vasoactive Intestinal Polypeptide Antiserum Affects Rat Prolactin mRNA in 40-Day but Not 110-Day Diethylstilbestrol-Induced Prolactinoma Tissue

Experiments were designed to examine whether vasoactive intestinal polypeptide (VIP), a known stimulator of basal prolactin (PRL) secretion, regulates PRL gene expression in the rat diethylstilbestrol (DES)-induced prolactinoma model. The VIP-induced increase in PRL release could result from increased PRL synthesis and/or decreased PRL degradation. Male Fischer 344 rats were implanted with 10 mg DES pellets 40 or 110 days prior to obtaining the anterior pituitary glands for cell dispersal. Cells were incubated in 1:10 normal rabbit serum or VIP antiserum (AVIP). After incubation, cells were pelleted, washed, and pooled for total nucleic acid extraction. The rat PRL (rPRL) mRNA abundance was quantitated using a solution hybridization/ribonuclease protection assay. Supernatant was collected and analyzed for PRL content using radioimmunoassay. Results from this experiment reveal partial immunoneutralization of intrapituitary VIP significantly decreased PRL secretory rate by rapid reduction in rRPL mRNA in the 40-day tumors. However, in the 110-day tumors the rPRL mRNA steady-state levels were unchanged but the basal release of PRL continued to be decreased by AVIP. These results indicate VIP exerts its effects on PRL secretion through at least two mechanisms.