Effects of intracerebroventricular infusions of ghrelin on secretion of follicle-stimulating hormone in peripubertal female sheep

Abstract

Reproduction depends on mechanisms responsible for the regulation of energy homeostasis and puberty is a developmental period when reproductive and somatic maturity are achieved. Ghrelin affects the activity of the hypothalamo-pituitary-gonadal axis under conditions of energy insufficiency. An in vivo model based on intracerebroventricular (i.c.v.) infusions was used to determine whether centrally administered acyl ghrelin affects transcriptional and translational activity of FSH in peripubertal lambs and whether ghrelin administration mimics the effects of short-term fasting. Standard-fed lambs received either Ringer-Lock (R-L) solution (120µL h) or ghrelin (120µL h, 100µg day). Animals experiencing a short-term (72h) fast were treated only with R-L solution. In each experimental group, i.c.v. infusions occurred for 3 consecutive days. Immunohistochemistry, in situ hybridisation and real-time reverse transcription quantitative polymerase chain reaction analyses revealed that short-term fasting, as well as exogenous acyl ghrelin administration to standard-fed peripubertal lambs, augmented FSHβ mRNA expression and immunoreactive FSH accumulation. In addition to the effects of ghrelin on FSH synthesis in standard-fed animals, effects on gonadotrophin release were also observed. Acyl ghrelin increased the pulse amplitude for gonadotrophin release, which resulted in an elevation in mean serum FSH concentrations. In conclusion, the present data suggest that ghrelin participates in an endocrine network that modulates gonadotrophic activity in peripubertal female sheep.

The Role of the Gastric Hormones Ghrelin and Nesfatin-1 in Reproduction

“…On one hand, in healthy young men acute infusion with acyl ghrelin had no effect on FSH secretion [104]. On the other hand, in proestrus afternoon and metestrus ghrelin stimulated FSH secretion from pituitary tissue in vitro [97], 3 day long ghrelin administration in prepubertal lambs increased FSHβ mRNA expression, FSH accumulation, and FSH serum levels [99], and similarly, 16 week long treatment with desacyl ghrelin elevated FSH in plasma [105]. This data points towards a dependency of ghrelin-induced FSH stimulation on timing and duration of administration.…”

“…In peripubertal lambs, ghrelin injections increased the pulse amplitude for gonadotrophin release [99]. In addition, in female rodents it was shown that the estrous cycle affects ghrelin-induced firing modulation, since only GnRH-positive neurons in metestrus, not in proestrus, decreased firing rate and burst frequency in response to ghrelin [100].…”

“…Ghrelin's expression in the pituitary is higher compared to most other tissues [14,15] and is affected by sexual maturation [16] and pregnancy [13]. Conversely, ghrelin was shown to have a stimulatory effect on FSH expression [97,99,105] as well as an inhibitory effect on GnRH-induced FSH secretion [97,106,107], depending on timing and duration of ghrelin administration. On LH expression and GnRH-induced LH secretion, ghrelin has a more consistent inhibitory effect [97,104,106,110,114], also reducing circulating LH levels [104,107].…”

Brain-Derived Neurotrophic Factor Affects mRNA and miRNA Expression of the Appetite Regulating Centre in the Sheep Arcuate Nucleus

“…no SC-4554) in a dose of 10 μg per day (BDNF 10 group; n = 8), and group II received BDNF in a dose of 60 μg per day (BDNF 60 group; n = 8), both diluted in 480 µL of Ringer-Locke solution, at an infusion rate of 120 µL h -1 . The doses of BDNF used in this experiment were chosen on the basis of information from the literature (Dittrich et al, 1996), our previous experience concerning the action of other peptides engaged in modulation of the hypothalamic energy centre such as leptin, ghrelin or obestatin in the sheep hypothalamus (Hasiec et al, 2017;Tillet et al, 2010;Wójcik-Gładysz et al, 2018, 2016Szlis et al, 2015), as well as preliminary studies (Szlis et al, 2018 b;Przybył et al, 2018).…”

Molecular regulation of follicle-stimulating hormone synthesis, secretion and action

“…This study identifies a novel pathway of gonadotropin secretion mediated by the adrenal cortex (Aleknaviciute, et al 2016). Ghrelin, a neuropeptide involved in the regulation of physiological energy balance, was also found to influence FSH secretion in pre-pubertal sheep (Wojcik-Gladysz, et al 2016). The identification of novel factors from such diverse physiological pathways indicates the complexity of FSH regulation.…”