Simultaneous Increases of Leptin and Gonadotropin-Releasing Hormone Following Exogenous Estrogen Administration in Women with Normally Menstrual Cycle

Abstract

Abstract. The aim of this study was to investigate whether administration of exogenous estrogen affects the changes of leptin and GnRH levels in women with normal menstrual cycle. A total of 18 women received a bolus intravenous injection of 20 mg conjugated estrogen (premarin group) at 0800 during the fifth day of menstrual cycle, while another 18 women were administered 20 mL of normal saline as the control group. Fasting blood samples were collected at 0,4,8, 24, 28, 32, 48, 56, 72 and 96 hours after injection for analyses of leptin, GnRH, estrone (E 1 ), estradiol (E 2 ), LH and FSH. Both the mean plasma levels of E 1 and E 2 were significantly increased from 4 hours and significantly sustained elevated levels up to 72 hours after injection of premarin. Simultaneous significant increases of leptin and GnRH levels were observed at 28, 32 and 48 hours after injection, while the controls remained constant. The mean LH and FSH levels were initially suppressed and then significantly increased at 56 and 72 hours after premarin administration. Leptin appears to be involved in the regulation of positive feedback mechanism of estrogen by conveyance of metabolic signal to affect the release of GnRH in hypothalamus, while its participation in the modulation of negative feedback remains unknown. LEPTIN, a novel adipocyte-derived hormone [1], has been recognized as a metabolic signal to the reproductive system because ob/ob mice showed significantly elevated serum levels of luteinizing hormone (LH) and increased ovarian and uterine weight after treatment with leptin [2]. Leptin can prevent the reduced pulsatile LH secretion during fasting by conveying some information about nutrition to the hypothalamus which releases a pulsatile gonadotropin-releasing hormone (GnRH) secretion [3] and can induce a dose-related increase in gonadotropin and GnRH release from the cultures of pituitary and hypothalamic cells in adult rats [4]. In addition, in our previous study of female transgenic skinny mice, sustained overexpression of leptin results in accelerated puberty and late-onset hypothalamic hypogonadism [5]. Therefore, leptin may play a role as a mediating signal of nutrition to affect the gonadotropin release by modulation of pulsatile GnRH secretion in hypothalamus [3][4][5]. On the other hand, a positive relationship between estrogen and leptin has been suggested. Leptin was found to be increased after addition of estrogen in the cultures of isolated human [6] and rat [7] adipocytes and also was found to be increased in women undergoing controlled ovarian hyperstimulation for assisted reproduction [8,9]. These women had high levels of estrogen, and the data strongly indicated that estrogen has a stimulatory effect on the production of leptin from adipose tissue. Exogenous estrogen administration is usually utilized in a clinical testing for examination of positive and negative feedback effect; thus, the differentiation

Differential Expression of Leptin and Leptin Receptor mRNA in Obese and Non-Obese Women across the Menstrual Cycle Title

“…Similar to the results of this study, our findings demonstrate that in obese women, leptin is directly related to FSH during the follicular phase (p < 0.001), and to testosterone in the late luteal phase (p < 0.001). Our findings lead us to concur with Lin et al [17], in their assertion that leptin must be somehow involved in the positive feedback regulation mechanism of estrogen by conveying a metabolic signal affecting the release of GnRH in hypothalamus, while its participation in the modulation of negative feedback remains unknown. However, whether or not leptin participates in the modulation of negative feedback mechanisms remains unknown.…”

“…These investigators concluded that leptin levels change during the menstrual cycle and that leptin levels are most stable on days 1 -5 of the cycle. In another study, Lin et al [17], administrated intravenous injections of 20 mg conjugated estrogen (premarin) in 18 women with normal menstrual cycles on the fifth day of their cycle in order to evaluate whether or not estrogen affects levels of leptin and GnRH. They found that both the mean plasma levels of estrone, estradiol, were significantly increased four hours after injection and these significantly elevated levels were sustained for up to 72 hours after the injection of premarin.…”

Correlation between estrogens and serum adipocytokines in premenopausal and postmenopausal women

“…It has been suggested that leptin may be involved in the regulation of a positive feedback mechanism with estrogen as a metabolic signal that affects the release of gonadotropin-releasing hormone by the hypothalamus. 42 In an in vitro study, E 2 stimulated leptin release in women`s adipose tissue, but E 1 had no effect on leptin release. 43 Our results suggest that leptin might stimulate plasma gonadotropin-releasing hormone levels to increase, which might result in a significant positive correlation with estrogens (E 1 and E 2 ) in premenopausal women but not in postmenopausal women after adjustment for BMI.…”

The Relationship between Maternal Plasma Leptin Levels and Fetal Growth Restriction

“…LEPTIN is a peptide hormone that regulates energy homeostasis, reproductive functions, and immune reactions [1][2][3][4][5]. Leptin is mainly produced in the adipose tissue in non-pregnant human subjects [6][7][8] and its production is augmented by increased adiposity [6,9].…”