Effects of leptin on basal and GHRH-stimulated GH secretion from the bovine adenohypophysis are dependent upon nutritional status

Abstract

We have shown recently that leptin modulates at least two aspects of anterior pituitary LH release in ruminants: basal and GnRH-mediated release. To test the hypothesis that leptin directly affects basal and GHRH-mediated GH secretion from the adenohypophysis, we examined the effects of various doses of recombinant ovine leptin (oleptin) on perifused adenohypophyseal (AP) explants and compared responses of tissues from control and fasted cows. Ten mature, ovariectomized and estradiol-implanted cows were assigned to one of two dietary groups: (1) normal-fed (n=5) and (2) fasted for 72 h (n=5). At the end of the fasting period, cows were euthanized and pituitaries were collected. Adenohypophyseal explants were perifused for a total of 6·5 h, including a 2-h treatment at 2·5 h with Krebs-Ringer bicarbonate buffer containing 0, 5, 10, 50, or 100 ng/ml oleptin, and a challenge with GHRH at 4·5 h. All doses of oleptin greater than 5 ng/ml decreased (P,0·01) basal GH secretion compared with controls in tissues collected from normal-fed cows. In contrast, GH release from AP explants from fasted cows treated with the lowest dose of oleptin was 28% (P,0·002) higher than control explants, but larger doses had no effect. Leptin caused an inversely related, dose-dependent increase in GHRH-mediated GH release in tissues from normal-fed cows. Marked increases (P,0·01-P,0·001) in GH release were observed for the 5 and 10 ng/ml oleptin, with lesser (P,0·08) and no effects observed at the 50 and 100 ng/ml doses respectively. In fasted cows, oleptin had no stimulatory effect on GHRH-induced GH release. Results show that leptin can act directly at the anterior pituitary level to modulate GH release, and this effect is dependent upon nutritional history.

The effect of intracerebroventricular infusion of leptin on the secretory activity of the somtotropic axis in fasted prepubertal lambs

“…Analogous effects of leptin on GH gene expression in somatotrophic cells were found in pigs . Our results are also comparable with those of in vitro studies where leptin-treated adenohypophyseal cell cultures from pig, cattle or rats exhibited a marked increase in basal secretion of GH (Barb et al, 1998;Cocchi et al, 1999;Zieba et al, 2003). The direct relationship between leptin and GH was additionally established by information about the presence of leptin receptors on the level of somatotrophic cells in the pituitary gland in sheep (Iqbal et al, 2000).…”

Leptin stimulates pituitary prolactin release through an extracellular signal-regulated kinase-dependent pathway

“…The authors suggested that the apparent insensitivity of the cells to nanomolar concentration of leptin could be explained by the use of heterologous human and mouse hormone respectively. In addition to its effect on gonadotropes, leptin has also been shown to regulate release of GH and PRL from isolated adenohypophysis preparations in rodents and cows ( Yu et al 1997, Zieba et al 2003. In other vertebrates, data are largely lacking, although one study has shown that micromolar concentrations of leptin stimulate somatolactin release by sixfold during the initial hours of treatment in European sea bass (Peyon et al 2003).…”

Leptin Stimulates Growth Hormone Secretion via a Direct Pituitary Effect Combined with a Decreased Somatostatin Tone in a Median Eminence-Pituitary Perifusion Study

“…Results of previous studies looking for an interaction between leptin and GHRH on secretion of GH from pituitary have been inconsistent. Leptin has been reported to increase or to have no effect on GHRH-stimulated GH secretion [26, 36, 38]. This fact may be due, in part, to different technical approaches that affect fundamental physiological characteristics of somatotropes maintained in vitro in short-term perifusion systems compared with long-term static primary culture.…”