Effects of leptin on gonadotropin secretion in juvenile female rat pituitary cells

Abstract

Objective: Leptin is an adipocyte-derived hormone, which is the product of the obese gene and it is thought to play important roles in pubertal development and maintenance of reproductive function in the female. In a study using adult male or female rats, it was found that leptin stimulated the secretion of gonadotropin directly from the pituitary in a dose-related manner. However, there is no study in juvenile female rats before puberty. Methods: In this study, we cultured pituitary cells from 4-, 6-and 8-week-old female Wistar rats with leptin (0 -10 27 mol/l) and gonadotropin-releasing hormone (GnRH) (0 or 10 28 mol/l). Basal or GnRH-stimulated secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and their synthesis within cells were determined by radioimmunoassay (RIA). Results: Leptin induced bell-shaped dose -response curves of basal LH and FSH secretion from cultured cells of every age-group of rats studied. The most effective concentration of leptin on the basal secretion of LH and FSH from 6-and 8-week-old cultured pituitary cells was 10 210 mol/l. This leptin concentration was consistent with circulating physiological serum leptin levels at each age. As for juvenile 4-week-old pituitary cells, the most effective concentration was 10 211 mol/l which was lower than that of 6-and 8-week-old rats. It was consistent with the circulating serum leptin levels of 4-week-old rats. Also, the synthesis and the GnRH-stimulated secretion of LH and FSH were effectively controlled by leptin at concentrations similar to the serum leptin levels of given ages. Conclusions: Leptin induced pituitary cells to synthesize and secrete both LH and FSH regardless of the presence or absence of GnRH. The concentration of leptin that induced the greatest synthesis and secretion of gonadotropins from pituitary cells changed around the pubertal period. The most effective leptin concentrations in each experiment were similar to the physiological serum leptin level at each animal age. These results indicate that leptin stimulates gonadotrophs not only in the pubertal and the mature period but also in the juvenile period before puberty. It is also conceivable that leptin may modulate the sensitivity of gonadotrophs until the appearance of GnRH stimulation, and may be the factor that brings about puberty onset.

In vitro effect of leptin on anterior pituitary cells LH secretory activity during early pregnancy in pig

“…However, in another study on prepubertal barrows/gilts, leptin only at 10 -8 and 10 -7 M concentration evoked a stimulatory LH response (Nanoka et al 2006). Also in vitro studies revealed that, at concentration from 10 -11 M to 10 -7 M of leptin increased basal LH release from juvenile female rat AP cells and observed effects showed a bell-shaped dose-response curve (Tezuka et al 2002). In our present study, however, a culture-specific pattern of response for different leptin concentrations was observed with a 10 -6 M being effective in LH basal release stimulation in four individual pituitaries-derived cultures.…”

“…LH-activating leptin activity was also reported in anterior pituitary cells of female (Ogura et al 2001, Tezuka et al 2002 and male (Yu et al 1997) rat hemi-anterior pituitaries. Pro-gonadotrophic stimulation was also shown in female rats at the time of spontaneous and steroid-induced LH surge (De Biasi et al 2001) and leptin concentrations maximally effective in basal LH release stimulation were similar to levels in juvenile, pubertal and mature female rats serum (Ogura et al 2001, Tezuka et al 2002.…”

“…Opposite results were reported in rats in which increase of basal and GnRH-induced cellular LH level was dependent on applied leptin concentration (Ogura et al 2001, Tezuka et al 2002 with 10 -10 M being effective in basal whereas 10 -10 , 10 -9 and 10 -8 M in GnRH-induced stimulation of intracellular LH accumulation (Ogura et al 2001). An existing differences between studies concerning gonadotrope cells response for exogenous leptin stimulation may result both from age and reproductive/endocrine status of tested animals, their metabolic state as well as from specific applied experimental protocol (e.g.…”

“…Furthermore, stimulatory influence of leptin on GnRH-induced LH release from AP pituitary cells was reported in juvenile (Tezuka et al 2002) and pubertal (Ogura et al 2001) rats and observed effect expressed as a bell-shaped dose-response curve. No leptin activity was found in respect to the In vitro effect of leptin on anterior pituitary cells LH...modulation of LH release from GnRH-activated hemi-anterior pituitaries of adult male (Yu et al 1997) as well as proestrus rats (Peters et al 2009).…”

Pituitary Leptin-A Paracrine Regulator of Gonadotropes: A Review

“…Thus, the literature suggests that leptin stimulates the secretion of both Luteinizing hormone (LH) and Gonadotropin releasing hormone (GnRH) either directly or indirectly [58,64,[67][68][69]. Leptin also restores LH secretion in fasted mice, rats, hamsters and monkeys [14-17, 20, 58, 64, 67, 68].…”