Direct effects of growth hormone (GH)-releasing hexapeptide (GHRP-6) and GH-releasing factor (GRF) on GH secretion from cultured porcine somatotropes

Sanchez-Hormigo, Angela; Castaño, Justo P.; Torronteras, Rafael; Malagón, Marı́a M.; Ramirez, José Luis; Gracia‐Navarro, Francisco

doi:10.1016/s0024-3205(99)80004-6

Cited by 14 publications

(2 citation statements)

References 24 publications

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“…Second, GHS, like GHRH, consistently stimulate GH secretion two-to fivefold by pituitary cells in vitro (7,12,13,70,71,89). Unlike GHRH, GHS and ghrelin induce GH gene expression only upon prolonged delivery to the infantile rat in vivo or to somatotropes in vitro (42,54).…”

Section: Ghrelin and Gh Network: Basis Of Model Structurementioning

confidence: 99%

“…GHRH potentiates feedforward drive by GHS because passive immunoneutralization or pharmacological antagonism of GHRH and truncational mutation of the GHRH receptor attenuate GHS-evoked GH secretion markedly in the rat, mouse, and human (31,35,63,65,68,78). In contradistinction, GHS and GHRH do not synergize in vitro (70,89). Pituitary portal vein sampling studies have indicated that GHS infusion elicits ArC GHRH release in the conscious sheep (31,35).…”

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confidence: 99%

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Deterministic construct of amplifying actions of ghrelin on pulsatile growth hormone secretion

Farhy

Veldhuis

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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(GHS) receptor that stimulates pulsatile GH secretion markedly. At present, no formal construct exists to unify ensemble effects of ghrelin, GH-releasing hormone (GHRH), somatostatin (SRIF), and GH feedback. To model such interactions, we have assumed that ghrelin can stimulate pituitary GH secretion directly, antagonize inhibition of pituitary GH release by SRIF, oppose suppression of GHRH neurons in the arcuate nucleus (ArC) by SRIF, and induce GHRH secretion from ArC. The dynamics of such connectivity yield self-renewable GH pulse patterns mirroring those in the adult male and female rat and explicate the following key experimental observations. 1) Constant GHS infusion stimulates pulsatile GH secretion. 2) GHS and GHRH display synergy in vivo. 3) A systemic pulse of GHS stimulates GH secretion in the female rat at any time and in the male more during a spontaneous peak than during a trough. 4) Transgenetic silencing of the neuronal GHS receptor blunts GH pulses in the female. 5) Intracerebroventricular administration of GHS induces GH secretion. The minimal construct of GHS-GHRH-SRIF-GH interactions should aid in integrating physiological data, testing regulatory hypotheses, and forecasting innovative experiments. somatotropic axis; growth hormone secretagogues; feedback; mathematical model; hormone pulsatility; hypothalamus; pituitary GHRELIN AND SYNTHETIC GROWTH HORMONE SECRETAGOGUES (GHS) stimulate pulsatile growth hormone (GH) secretion via combined hypothalamohypophyseal mechanisms. The GHS receptor is expressed by somatotrope cells and arcuate nucleus (ArC) neurons containing GHRH and other peptides (40,44). Ghrelin and GHS act directly on GH-secreting (somatotrope) cells and indirectly on the inhibitory signal somatostatin (SRIF) and the peptidyl agonist GH-releasing hormone (GHRH) (13,27,44,51). In particular, GHS stimulate somatotropes in vitro but are synergistic with GHRH, induce ArC GHRH release, and antagonize certain hypothalamic actions of SRIF in vivo (3,10,13,27,37,40,51). GHRH potentiates feedforward drive by GHS because passive immunoneutralization or pharmacological antagonism of GHRH and truncational mutation of the GHRH receptor attenuate GHS-evoked GH secretion markedly in the rat, mouse, and human (31,35,63,65,68,78). In contradistinction, GHS and GHRH do not synergize in vitro (70, 89). Pituitary portal vein sampling studies have indicated that GHS infusion elicits ArC GHRH release in the conscious sheep (31, 35). Other experiments have established that GHS can oppose inhibition by SRIF and octreotide in the anterior pituitary gland and the hypothalamus (25)(26)(27)71). No formalism incorporates these multilocus actions of GHS into available constructs of self-renewable GH pulses mediated by GHRH-SRIF-GH feedback interactions (34,53,61,72).Current models of the basic properties of the GH pulse renewal process assume reciprocal interactions among GHRH, SRIF,. In the present work, we have used this foundation in an effort to incorporate the known effects of GHS in a simple network-l...

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