Decrease in Luteinizing Hormone Pulse Frequency during a Five-Hour Peripheral Ghrelin Infusion in the Ovariectomized Rhesus Monkey

Abstract

Ghrelin, a nutrition-related peptide secreted by the stomach, is elevated during prolonged food deprivation. Because undernutrition is often associated with a suppressed reproductive axis, we have postulated that increasing peripheral ghrelin levels will decrease the activity of the GnRH pulse generator. Adult ovariectomized rhesus monkeys (n = 6) were subjected to a 5-h iv human ghrelin (100- to 150-microg bolus followed by 100-150 microg/h) or saline infusion, preceded by a 3-h saline infusion to establish baseline pulsatile LH release. Blood samples were collected at 15-min intervals throughout the experiment. Ghrelin infusion increased plasma ghrelin levels 2.9-fold of baseline. Ghrelin significantly decreased LH pulse frequency (from 0.89 +/- 0.07/h in baseline to 0.57 +/- 0.10/h during ghrelin infusion; P < 0.05, mean +/- sem), whereas LH pulse frequency remained unchanged during saline treatment. LH pulse amplitude was not affected. Ghrelin also significantly stimulated both cortisol and GH release, but had no effect on leptin. We conclude that ghrelin can inhibit GnRH pulse activity and may thereby mediate the suppression of the reproductive system observed in conditions of undernutrition, such as in anorexia nervosa. Ghrelin also activates the adrenal axis, but the relevance of this to the inhibition of GnRH pulse frequency remains to be established.

The effect of intracerebroventricular infusions of ghrelin on the secretory activity of the GnRH/LH system in peripubertal ewes

“…Furthermore, in hypothalamic fragments isolated from ovariectomised female rats, ghrelin significantly suppressed GnRH secretion (Fernández-Fernández et al, 2005b). The suppressive effect of ghrelin on reproductive activity due to the impairment of GnRH pulsatility was also reported in ovariectomised rhesus monkeys (Vulliémoz et al, 2004). Thus, the GnRH pulse generator appears to be the predominant target of ghrelin activity at the hypothalamic level.…”

“…The ability of ghrelin to inhibit LH secretion appeared not to be dependent on the steroid hormone concentration, since this effect was observed at all stages of the oestrous cycle, as well as in ovariectomised female rats (Fernández-Fernández , 2005a). In adult ovariectomised monkeys or sheep, central or peripheral administration of ghrelin down-regulated LH release (Vulliémoz et al, 2004;Iqbal et al, 2006). Similarly, reduction of pulse amplitude and frequency without changes in mean LH concentration was observed in oestradiolimplanted castrated male sheep (Harrison et al, 2008).…”

Ghrelin and reproductive disorders

“…The effects of ghrelin upon gonadotropins and PRL secretion have been explored in a limited number of models and animal species, including rats, primates and sheep (Fernández-Fernández et al, 2004;Fernández-Fernández et al, 2005a;Furuta et al, 2001;Harrison et al, 2008;Iqbal et al, 2006;Kluge et al, 2007;Lanfranco et al, 2008;Vulliémoz et al, 2004). These studies showed that central administration of ghrelin suppressed pulsatile LH secretion in ovariectomized female rats (Furuta et al, 2001).…”

Pituitary Leptin-A Paracrine Regulator of Gonadotropes: A Review

“…Investigators have shown that ghrelin had inhibitory effects on LH and mixed effects on reproductive functions, depending on sex and physiological state [141][142][143]. Other workers showed reductions in LH pulse frequency in rats [144] or humans [145]. Recently, Iqbal et al [146] reported that an i.c.v.…”

“…The higher ghrelin might thus be responsible for the mediation of the lower pituitary leptin. Furthermore, if pituitary (somatotrope) leptin is important for gonadotrope function through paracrine mechanisms, lowering somatotrope leptin might contribute to the lower LH or reduced pulses of LH [145].…”