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

Abstract

The aim of this study was to examine the effect of recombinant human leptin on growth hormone (GH) secretion in perifused anterior pituitary slices from adult pigs. Anterior pituitary slices from sows were perifused and treated with recombinant human leptin (10 nM) and GH-releasing hormone (GHRH; 1 nM). In some experiments, pituitary slices were coincubated with stalk median eminence (SME). In a subset of the coincubation experiments, immunoneutralization of endogenous GHRH and somatostatin (SRIH) release was performed with antisera to GHRH and SRIH. Leptin increased GH secretion in pituitary slices alone (up to 100% vs. control at 40 min) as well as in pituitary slices coincubated with SME (up to 122% vs. control at 40 min). A significant difference was observed in GH secretion from pituitary slices when the tissue was coincubated with leptin and GHRH at a low concentration (0.1 nM), but not when GHRH was used at 1 and 10 nM. Furthermore, anti-SRIH antiserum increased GH release from pituitary slices in coincubation experiments with SME. Finally, SRIH secretion was significantly reduced by leptin (down by 35% vs. control from 0 to 30 min of treatment) in cultured SME. These data show that leptin is effective in stimulating GH secretion by acting at two different levels: (1) it stimulates GH secretion directly from pituitary slices, and (2) it reduces SRIH tone from the median eminence and, indirectly, increases GH secretion from the pituitary. These results support the hypothesis that leptin may be an interesting hormonal mediator of growth and related metabolic effects by acting directly on the hypothalamic-pituitary axis.

Leptin inhibits swallowing in rats

“…On the contrary, the highest doses (6 ϫ 10 Ϫ9 M) used in the initial experiments for detecting a possible action of leptin belong to the pharmacological domain. It must be emphasized that, in works using the patch-clamp technique on hypothalamic slices, leptin is currently perfused at 10 Ϫ6 to 10 Ϫ11 M (30,36,38,40). Leptin receptors are abundant in the lower brain, and particularly in the dorsal vagal complex, which includes the STN (18,22).…”

Effects of maternal nicotine exposure on thyroid hormone metabolism and function in adult rat progeny

“…Interestingly, this understimulated pituitary, when incubated in vitro, releases more TSH than control pituitaries, indicating that some in vivo inhibitory factor is acting on the offspring of NIC dams (e.g., somatostatin). In fact, it has been demonstrated that leptin inhibits somatostatin in hypothalamic cultures (Saleri et al 2004).…”

Serum leptin concentrations in adolescents and young adults with growth hormone deficiency

“…Wywiera ona także wielokierunkowe działanie na funkcjonowanie ośrodkowego układu nerwowego, wpływając na nastrój, emocje i procesy poznawcze [11,12]. LEP działa modulująco na wydzielanie horonów przysadkowych, stymulując wydzielanie TRH, GnRH, GH, PRL oraz hamując sekrecję ACTH [12][13][14]. W układzie sercowo-naczyniowym LEP może działać kardioprotekcyjnie, zmniejsza rów-nież toksyczne działanie lipidów zgromadzonych poza tkanką tłuszczową, w tym również w myocardium [15,16].…”

“…Pomimo że leptyna moduluje wydzielanie hormonów przysadki, to jej prawidłowa czynność nie jest niezbędna do zachowania dobowego profilu wydzielania LEP [12][13][14]49].…”