Sex Steroid Hormones Regulate Leptin Transcript Accumulation and Protein Secretion in 3T3-L1 Cells

Abstract

Leptin is an adipokine produced by fat cells that regulates food consumption and metabolic activity. Sexual dimorphism in leptin and fat stores have been observed in humans and rodents with females having more leptin and greater levels of subcutaneous fat than males. One potential mechanism leading to this dimorphism is steroid hormone regulated synthesis of transcripts encoding leptin. Identification of direct regulatory mechanisms is difficult in animals or primary adipocytes due to these intertwined dimorphisms. We used well-characterized 3T3-L1 murine adipocytes to demonstrate that dihydrotestosterone (DHT) reduced Leptin (Lep) transcript abundance and cytosolic and secreted leptin protein. The magnitude of this effect was greatest on secreted leptin, which was decreased by DHT to 30% of the control. In contrast, 17β-estradiol significantly increased the abundance of transcripts encoding leptin and increased secreted leptin to 230% of the control. Treatment with estrogen and androgen receptor antagonists had opposite effects on Lep transcript abundance to steroid treatments, indicating that these transcriptional effects are mediated through the canonical steroid hormone signaling pathways. These results indicate that short-term treatments with steroid hormones are sufficient to alter both Lep transcript accumulation and leptin protein secretion, and may play a role in the sexual dimorphism of this adipokine.

Increased Expression of the Leptin Gene in Adipose Tissue of Patients with Chronic Kidney Disease–The Possible Role of an Abnormal Serum Fatty Acid Profile

“…Adipose tissue is a highly heterogeneous organ with cell-and depot-specific functions [35][36][37]. However, we chose 3T3-L1 differentiated adipocytes because they are a well-characterized and widely used cell line in metabolic, molecular, and endocrine studies, including studies on leptin expression levels [38][39][40][41].…”

Sex Differences in Liver, Adipose Tissue, and Muscle Transcriptional Response to Fasting and Refeeding in Mice

“…It is possible that increased levels of leptin in the blood of females were associated with the action of sex hormones. It has been demonstrated that testosterone reduces the concentration of leptin [35], and estrogen increases leptin production in vivo [36] and in vitro [37]. Perhaps the sex-specific insulin response to food intake is a common phenomenon for different species: Men also have significantly higher postprandial insulin levels compared to women [19].…”

Reproductive phase-dependent variation, sexually dimorphic expression and sex steroids-mediated transcriptional regulation of lep and lepr in lymphoid organs of Channa punctata

“…Sex steroids, depending on dose, had either inhibitory or no effect on lep and lepr expression in primary as well as secondary lymphoid organs of both the sexes, except on lepr in head kidney where DHT had marked stimulatory effect in male and E 2 in female. Since the effect of sex steroids on lep and lepr expression remain unexplored in immune organs of vertebrates, we analysed our results in light of observations in other tissues of fishes 26,28,29 and mammals 41,[50][51][52][53][54] . Our findings on lep and lepr expression in immune organs of C. punctata are largely contrasting to a recent study in immature male Salmo salar in which testosterone is reported to increase lep expression in liver and pituitary while plasma level of leptin has been shown to remain unchanged in androgen-treated fish 28 .…”

“…In contrast, male as well as female sex steroids have been demonstrated to downregulate the expression of lep and its receptor in hepatocytes of immature female Cynoglossus semilaevis 31 . Apart from fishes, direct role of sex steroids has been explored also in mammals where androgens and estrogen are shown to have differential effects, inhibitory, stimulatory or no effect, on leptin production from adipocytes 18,[52][53][54] . Surprisingly, in vitro study to demonstrate the effect of sex steroids on expression of leptin receptor is missing in mammals.…”