Melatonin Administration Accelerates Puberty Onset in Mice by Promoting FSH Synthesis.

Chan Yang,Chuqi Ling,Changjiu He,Zaohong Ran,Rong Hou,Xiang Li,Qinghua Liu,Xiaodong Wang,Yingjun Chen,Yuliang Liu,Guoshi Liu,Fang Fang

doi:10.3390/molecules26051474

Abstract

Although melatonin has been extensively studied in animal reproduction, the mechanism of melatonin in puberty remains elusive. This study was designed to explore the effect of intraperitoneal administration of melatonin on puberty onset in female mice. The injection of melatonin into postnatal days 10 mice at a dose of 15 mg/kg accelerated the puberty onset in mice. Mechanistically, there was no difference in physical growth and serum Leptin levels after melatonin administration. Meanwhile, the serum levels of reproductive hormones involved in hypothalamic-pituitary-ovarian axis, such as FSH and estrogen level in serum were increased. The mRNA levels of GnRH and GnRHr were not affected by melatonin, while the expressions of FSHβ in pituitary and Cyp19a1 in ovary were significantly up-regulated. In addition, melatonin still promoted FSH synthesis after ovariectomy. Furthermore, the enhanced activity of ERK1/2 signaling verified that the expression of FSHβ increased in pituitary. We confirmed that melatonin promoted the FSH synthesis in pituitary, thereby increased serum estrogen levels and ultimately accelerated puberty onset. However, these effects of melatonin may be pharmacological due to the high dose. This study would help us to understand the functions of melatonin in pubertal regulation comprehensively.

Highlights

Melatonin (MLT) is synthesized mainly in the pineal gland related to the control of the circadian rhythm [1] and seasonal reproduction [2]
Further studies showed that melatonin regulates the secretion of FSH and luteinizing hormone (LH) mainly through the hypothalamus-pituitary-gonadal axis and affect the secretion of gonadal reproductive hormones, or directly acts on ovarian melatonin receptors to regulate the secretion of steroid sex hormones [9,10]
The results indicated that the average day of puberty onset in melatonin-treated group was significantly earlier than that in control group (24.48 ± 0.21 vs 25.32 ± 0.17, p < 0.05), respectively (Figure 1B)

Summary

Introduction

Melatonin (MLT) is synthesized mainly in the pineal gland related to the control of the circadian rhythm [1] and seasonal reproduction [2]. Melatonin is a wellknown effective antioxidant which served as a scavenger of free radicals or a metabolite playing a cascade amplification of antioxidant effects in cells [3]. Melatonin plays an important role in reproductive hormone secretion, oocyte quality, luteal function, ovulation, and early embryonic development [7,8]. Secretion of luteinizing hormone (LH) before ovulation can result in high expression of MTI in ovarian granulosa cells. The level of progesterone in mouse follicles significantly increases when treated with melatonin in vitro [15]. The addition of exogenous melatonin significantly mitigated the oxidative damage of matured bovine oocytes [16], and prominently improved the developmental potential of fertilized embryos in vitro [17]

Methods

Results

Discussion

Conclusion