Inhibitory Action of Leptin on Early Follicular Growth Differs in Immature and Adult Female Mice

Abstract

In order to investigate the action of leptin on early follicular growth, preantral follicles, 95-115 microm in diameter were mechanically isolated from the ovaries of BDF1 hybrid immature (11-day-old) and adult (8-wk-old) mice, and cultured for 4 days in vitro. Follicular growth was assessed by daily changes in follicular diameter and by the amount of estradiol and immunoreactive (IR)-inhibin released into the culture medium at Day 4. Preantral follicles from immature mice showed a significant development in follicular growth as a result of stimulation by GH (1 mIU/ml), insulin-like growth factor (IGF)-I (100 ng/ml) + FSH (100 mIU/ml), and GH (1 mIU/ml) + FSH (100 mIU/ml). Although leptin at concentrations of 1-1000 ng/ml did not have any significant effect on follicular growth stimulated by IGF-I or GH, it significantly inhibited follicular growth in a dose-related manner when follicles were stimulated by IGF-I + FSH and GH + FSH, respectively, suggesting that leptin attenuated the additive effect of FSH. On the other hand, preantral follicles from adult mice were cultured in the presence of FSH, and FSH-dependent follicular growth was inhibited by leptin in a dose-related manner. Because FSH stimulates cAMP production, we investigated the involvement of cAMP in the inhibitory mechanisms of leptin. Preantral follicles from immature and adult mice were cultured in the presence of either 8-Br-cAMP or forskolin. Both 8-Br-cAMP and forskolin significantly increased follicular diameter and hormone secretion in both immature and adult mice. However, 8-Br-cAMP and forskolin-stimulated follicle growth and hormone secretion were significantly inhibited in immature mice by coadministration of leptin, whereas growth of preantral follicles from adult mice was not inhibited by addition of leptin to cultures. These results indicate that leptin causes an inhibitory effect on the early follicular development of both immature and adult mice, but the inhibitory mechanisms of leptin are different.

Leptin modulates the expression of its receptors in the hypothalamic–pituitary–ovarian axis in a differential way

“…In this work, we found that leptin is able to induce a biphasic effect on progesterone production. A direct inhibitory action of leptin on steroid hormone secretion has been demonstrated independently by different authors in the ovary (Spicer & Francisco 1997, Zachow & Magoffin 1997, Agarwal et al 1999, Barkan et al 1999, Zachow et al 1999, Ghizzoni et al 2001, Kikuchi et al 2001 and in other tissues (Tena-Sampere et al 2001, Cameo et al 2003. However, findings of both stimulation and inhibition effect with different levels of leptin in ovarian cells in vitro are in agreement with observations by Ruiz-Cortés et al (2003) who found that the effects of leptin are biphasic with regard to stimulation and inhibition of progesterone synthesis.…”

Continuous Melatonin Treatment and Fasting in the Raccoon Dog (Nyctereutes procyonoides) – Vernal Body Weight Regulation and Reproduction

“…Their leptin concentrations were high before the mating season and decreased before estrus, which occurred during the later half of March. In female rodents, leptin accelerates the onset of puberty (Ahima et al, 1997;Chehab et al, 1997) but inhibits early follicular development (Kikuchi et al, 2001) and ovulation (Duggal et al, 2000). The male and female raccoon dogs experienced a rise in their leptin levels during the winter before the vernal part of the experiment started simultaneously with the increasing plasma testosterone and luteinizing hormone levels connected to the approaching mating season (Asikainen et al, 2003).…”

Adiposity associated rise in leptin impairs ovarian activity during winter dormancy in Vespertilionid bat, Scotophilus heathi

“…Administration of leptin to obese leptin-deficient mutant mice increased ovarian activity and restoration of fertility (Barash et al 1996, Chehab et al 1996, Kikuchi et al 2001. A direct involvement of leptin in ovarian function has been postulated following the demonstration of leptin-receptors in the ovaries of numerous mammalian species (Karlsson et al 1997, Ruiz-Cortés et al 2000, Kikuchi et al 2001.…”