The aim of this study is to further investigate estrogen, corticoid, and gonadotropin abnormalities in obesity: (1) 24-hour mean plasma estrone (E1) and estradiol (E2) are evaluated in obese men but not obese women. The high estrogen levels in the men cause hypogonadotropic hypogonadism (Decreased FSH, relatively low LH, Decreased free and total testosterone). Giving dexamethasone (D) normalizes the hormone levels) (? suppresses adrenal secretion of Delta4-androstenedione (Delta), the main substrate of aromatization of estrogens). These studies will be extended in number and duration; we will also test whether the aromatase inhibitor testololactone similarly normalizes hormone levels. (2) D administration greatly decreases plasma E1, but not E2, in obse women. This suggests a large contribution of aromatization to E1 levels. The absence of elevated E1 levels despite this remains unexplained. It is not known whether nonobese women respond similarly to D suppression and this will be studied. (3) Weight loss unexpectedly increases plasma E2 in obese men. We will study the effects of duration and degree of weight loss, and initial and final weight, on this phenomenon. The effect of weight loss on plasma estrogen in obese women will also be studied. (4) Obese women have depressed 24-hour mean plasma LH and LH/FSH ratio, resembling the """"""""slow-GnRH-pulsing syndrome"""""""" in monkeys; these monkeys do not ovulate (? pertinent to frequent anovulation in obese women). 24-Hour plasma LH profile will be studied in normal and obese women to document LH-pulsing frequency (?=GnRH pulsing frequency). (5) The sex difference in plasma E2/E1 ratio (women greater than men) is accentuated in obesity. Kinetics of E1-E2 interconversion will be studied with tracers, using a newly devised protocol, under basal conditions and in two states of acute elevation of the E2/E1 ratio (infusion of E2 loads; E1 suppression by D). (6) Evidence has been found of a sex difference in adipose-tissue content of estrogen and corticosteroid receptor (women greater than men). In vitro quantitation of both types of receptors will be done and an indirect in vivo measure of estrogen receptor content will be made using tamoxifen: this drug increases urinary excretion of radioactivity from estradiol tracers in women (? blocks uptake by tissue receptor); if men have less receptor, tamoxifen should have less effect on tracer excretion.
| Strain, G W; Hershcopf, R J; Zumoff, B (1992) Food intake of very obese persons: quantitative and qualitative aspects. J Am Diet Assoc 92:199-203 |
| Zumoff, B; Strain, G W; Miller, L K et al. (1988) Partial reversal of the hypogonadotropic hypogonadism of obese men by administration of corticosuppressive doses of dexamethasone. Int J Obes 12:525-31 |
| Zumoff, B (1988) Hormonal abnormalities in obesity. Acta Med Scand Suppl 723:153-60 |
| Strain, G W; Zumoff, B; Miller, L K et al. (1988) Effect of massive weight loss on hypothalamic-pituitary-gonadal function in obese men. J Clin Endocrinol Metab 66:1019-23 |
| Miller, L K; Kral, J G; Strain, G W et al. (1987) Differential binding of dexamethasone to ammonium sulfate precipitates of human adipose tissue cytosols. Steroids 49:507-22 |
| Strain, G W; Strain, J J; Zumoff, B (1985) L-tryptophan does not increase weight loss in carbohydrate-craving obese subjects. Int J Obes 9:375-80 |
