Influence of Melatonin on Basal and Gonadotropin-Stimulated Progesterone and Estradiol Secretion of Cultured Human Granulosa Cells and in the Superfused Granulosa Cell System

Abstract

The aim of this study was to explore the direct action of melatonin (Me) on basal and gonadotropin-stimulated progesterone (PG) and estradiol (E₂) secretion of human granulosa cells (GCs) cultured in serum-free medium and in a superfused GC system. Human GCs were isolated from preovulatory follicular fluid aspirated from 34 women undergoing in vitro fertilization at the University Women’s Hospital of Tübingen. PG and E₂ production was measured in the presence and absence of Me, propranolol, LH or FSH using radioimmunoassay. Statistical analysis of the data was performed by ANOVA and Newman-Keuls test. Me stimulated E₂ secretion in a dose-dependent manner. Propranolol did not cause any change in E₂ secretion, and when given with Me, it only partially blocked but could not entirely prevent E₂ output. There was no statistically significant effect of Me on PG production when Me was administered at concentrations between 10^–4 and 10^–8 M. However, at 10^–3 M Me significantly suppressed PG output of granulosa cells. LH and FSH significantly stimulated the secretion of both steroid hormones. Me significantly reduced LH- and FSH-induced E₂ secretion, as well as LH-stimulated PG output, while it caused only a slight, yet significant decrease in PG secretion. In the superfused GC system, FSH and LH resulted in a significant stimulatory effect on PG release. Me did not modify the stimulatory effect of FSH on PG, while it caused some delay in LH-stimulated PG release. Propranolol and Me had no stimulatory effect on PG release. On the basis of our results we suggest that Me has a direct modulatory effect on basal E₂ and gonadotropin-stimulated E₂ and PG secretion of human GCs. The observed effect may play a physiological role in the regulation of GC function during the menstrual cycle.

Evidence of melatonin synthesis in the cumulus oocyte complexes and its role in enhancing oocyte maturation in vitro in cattle

“…In the present study, there was no significant effect of melatonin supplementation during IVM on the ability of bovine COCs to produce progesterone. In accordance with our results, some previous reports showed no or even negative effects of melatonin on progesterone production in growing and luteinized GCs (Battista and Condon, 1986; Brzezinski et al, 1987; Khan‐Dawood and Dawood, 1993; Sirotkin, 1994; Murayama et al, 1997; Schaeffer and Sirotkin, 1997; Tamura et al, 1998; Bódis et al, 2001; Nakamura et al, 2003). On the other hand, melatonin‐stimulated secretion was reported in previous studies (Crisp and Channing, 1972; Tureck and Strauss, 1982; Sugino et al, 2000; Woo et al, 2001; Tamura et al, 2009; Taniguchi et al, 2009).…”

Melatonin deprival modifies follicular and corpus luteal growth dynamics in a sheep model

“…Similarly, this effect has been described in many other species, including rats and sheep (Durotoye et al 1997, Adriaens et al 2006. On the contrary, some reports showed no effects or negative effects of melatonin on P 4 production in the growing and luteinised granulosa cells (Sirotkin 1994, Murayama et al 1997, Schaeffer & Sirotkin 1997, Bodis et al 2001, Nakamura et al 2003. The interpretation of studies on the in vitro effects of melatonin on steroidogenesis is complicated and seems to depend on cell types (theca or granulosa cells), duration of treatment (acute or long-term response), experimental model (cell culture or follicle culture), species, dose and different culture media (Tamura et al 2009).…”

Melatonin and the ovary: physiological and pathophysiological implications

“…Melatonin enhances hCG-stimulated P secretion from these cells, possibly by the elevated expression of the LH receptor. On the contrary, some reports showed no effects or negative effects of melatonin on P production in the growing and luteinized GCs (22,44,67,131,132). Sirotkin (131) documented that melatonin (1 ng/mL-100 mg/mL) inhibited P and cAMP secretion by GCs isolated from porcine ovaries.…”