In Vivo and in Vitro ob Gene Expression and Leptin Secretion in Rat Adipocytes: Evidence for a Regional Specific Regulation by Sex Steroid Hormones

Abstract

As a sexual dimorphism appears in plasma leptin levels, the aim of the present study was to investigate, in vivo and in vitro, the influence of sex steroid hormones on ob messenger RNA (mRNA) and leptin expressions in rat fat cells from various anatomical localizations. In male rats, castration resulted in a modulation of ob gene mRNA expression which was increased by 2-fold in perirenal and half-reduced in sc adipocytes. Moreover, in isolated fat cells from both perirenal and s.c. fat depots, ob gene mRNA expression was reduced by 20% after a 24-h in vitro exposure to dihydrotestosterone (10(-8) M). This effect of dihydrotestosterone on ob mRNA was prevented by exposure to the antiandrogen cyproterone acetate and also by actinomycin D. In contrast, leptin secretion from both perirenal and sc adipocytes was unchanged after 24 h exposure to dihydrotestosterone. In female rats, ovariectomy induced a 25% decrease in ob gene mRNA expression in perirenal fat cells. In vitro studies revealed that a 24-h exposure to 17-beta estradiol (10(-8) M) induced a 1.4-, 1.2-, and 1.75-fold increase in ob mRNA expression and a 3.8-, 1.65- and 2-fold increase in leptin secretion in sc, perirenal and parametrial adipocytes, respectively. Moreover, these effects were prevented by the antiestrogen ICI182780 and also by actinomycin D. Altogether, these results demonstrate that in rat adipocytes, estrogens, and androgens modulate ob gene expression at the mRNA level through sex steroid receptor-dependent transcriptional mechanisms.

Physiologic estradiol levels enhance hypothalamic expression of the long form of the leptin receptor in intact rats

“…This agrees with the failure of leptin levels to fall in hypophagic, underweight, estradiol-treated rats, which was observed previously [3], and gives support to the suggestion that estradiol has an independent stimulatory effect on leptin; indeed, estradiol enhances leptin synthesis and release in vitro [37]. Hypothalamic Ob-Rb mRNA was increased in the pairfed untreated group that lost weight, consistent with previous reports showing enhanced expression of Ob-Rb mRNA associated with decreased plasma leptin [38].…”

The gender- and fat depot-specific regulation of leptin, resistin and adiponectin genes expression by progesterone in rat

“…Based on these findings one can suppose that similar factors could be responsible for the observed increase of body weight. The lack of progesterone administration on the serum concentration of leptin and adiponectin despite significant increases of leptin and adiponectin gene expression in inguinal adipose tissue of female rats could be attributed to the fact that in females retroperitoneal, and in males retroperitoneal and epididymal WAT, are the main sources of the circulating leptin [39][40][41].…”

Estrogenic restoration of functional pancreatic islet cytoarchitecture in diabetes (db/db) mutant C57BL/KsJ mice: relationship to estradiol localization, systemic glycemia, and persistent hyperinsulinemia

“…Estrogen therapy modulated (blocked arrows) the endometabolic responses to the expressed db/db influences by reducing the severity of expression of the hyperglycemic, hypercytolipidemic, and cytodegenerative indices in C57BL/KsJ mice. tion, many of the common endometabolic disturbances (Garris 1999(Garris , 2004a and inflammatory cytokine cascades (Bruun et al 2003;Geisler et al 2002;Machinal et al 1999) shared by these DOS mutation expressions respond to E2-HRx, including the obesity and hyperglycemic components of the syndromes (Coleman 1985;Garris 2004a). These data suggest that the observed amelioration of the severe db/db indices following E2-HRx in the current studies was promoted by metabolic restoration of glucose metabolism in the absence of leptinmodulated caloric loading in this mutant.…”

“…Both estradiol (E2) and progesterone (P) are recognized to moderate the severity of the hyperglycemic-hyperinsulinemic state by reducing body mass, reestablishing normal glucose utilization rates, and reducing the severe hypercytolipidemia (Garris 1990a(Garris , 1999(Garris , 2004aGarris 2003a, b, 2004b;Garris et al 1985b;Kahn et al 1999;Machinal et al 1999;Morley 1988) and amyloidosis (Couce et al 1996;Kahn et al 1999) which promote pancreatic β-cell demise in this type 2 (NIDDM) model (Garris 2004a). Of particular interest was the promotion of normal pancreatic insulin levels in E2-HRx db/db mutants concurrent with the reestablishment of islet cell cytoarchitecture (Coleman 1985;Coleman et al 1984Coleman et al , 1982.…”