Effects of leptin on secretion of LH and FSH from primary cultured female rat pituitary cells

Abstract

Background: Leptin, which is the product of the obese gene, is believed to play important roles in pubertal development and reproductive function in females. In a study using adult male rats, it was found that leptin stimulated secretion of gonadotropin from the pituitary in a dose-related manner. However, there has been no such study in female rats. Objective: To investigate the effects of leptin on the production of LH and FSH from the pituitary in female rats, using primary cultured pituitary cells. Methods: In this study, we determined body weight, serum leptin concentration and serum estradiol (E 2 ) concentration in female Wistar rats at 3, 5, 6, 7, 9 and 11 weeks of age, and cultured pituitary cells from 6-week-old female Wistar rats with leptin (0±10 27 mol/l) and GnRH (0 or 10 28 mol/l). Then basal and GnRH-stimulated extra-and intracellular LH and FSH were assayed by RIA. Results: Serum leptin concentration increased with increases in body weight and E 2 concentration. The pubertal serum leptin concentration was about 10 210 mol/l. At a lower or moderate concentration, leptin produced dose-related increases in both basal and GnRH-stimulated extraand intracellular LH and FSH in pituitary cells. At a concentration of 10 210 mol/l, leptin significantly P , 0X05 stimulated both basal and GnRH-stimulated extra-and intracellular LH and FSH. However, at greater concentrations, these effects diminished. Conclusions: These results indicated that leptin induced pituitary cells to produce and secrete both LH and FSH, with or without GnRH. The concentration of leptin that induced the greatest production of gonadotropins by pituitary cells was 10 210 mol/l, which was the same as the physiological pubertal concentration. Leptin may be involved in the onset of puberty. It is also conceivable that leptin may be a cause of ovulatory failure, not only in weight loss but also in weight gain.

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

“…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

“…Interestingly, no changes were noted in hypothalamic GHRH levels themselves, which suggested that GHRH did not mediate the restoration. In addition, several in vitro studies showed that leptin directly stimulated LH secretion [70][71][72][73][74] and may stimulate or inhibit GH [23,68,76,77,79,80,88,114,[179][180][181][182][183][184], depending on experimental conditions. In light of these findings, we hypothesized that, if it was a paracrine regulator, pituitary leptin might itself be regulated by the nutrient status.…”

“…Leptin also restores LH secretion in fasted mice, rats, hamsters and monkeys [14-17, 20, 58, 64, 67, 68]. Leptin also directly stimulates LH secretion from pituitary cells in vitro [70][71][72][73][74]. In addition, leptin regulates Growth hormone (GH) [19], although there is lack of agreement about the exact direction of its regulation [19,[75][76][77][78].…”