Growth hormone (GH) autofeedback action in the neonatal rat: involvement of GH-releasing hormone and somatostatin

Abstract

It is known that in adult rats, GH by itself and by promoting secretion of the somatomedins acts at the level of the hypothalamus to trigger release of somatostatin and decrease output of GH-releasing hormone (GHRH), thereby inhibiting further secretion of GH. To assess whether these mechanisms are already operative in the early postnatal period, we have evaluated the effect of short-term administration of GH in 10-day-old rats. Twice-daily s.c. administration of 25 micrograms human GH/rat, from days 5 to 9 of life, significantly reduced pituitary content of GH, decreased hypothalamic levels of GHRH mRNA and abolished the in-vivo GH response to a challenge dose of GHRH (20 ng/100 g body weight, s.c.). GHRH (20 ng/100 g body weight, twice daily, s.c.) given concomitantly with the GH treatment, completely counteracted the inhibitory effect of the latter on pituitary content of GH and restored to normal the in-vivo GH response to the GHRH challenge. These data indicate that impaired secretion of GHRH is involved in the inhibitory effect elicited by GH treatment in infant rats. However, concomitant involvement of hypothalamic somatostatin as a result of GH treatment cannot be ruled out. In fact, pituitaries from rats pretreated with GH responded in the same manner as pituitaries from control rats to the GHRH challenge in vitro.

Clinical Implications of Growth Hormone Feedback Mechanisms

“…for 5 days induced a 35% decrease of GHRH mRNA in the hypothalamus, decreased pituitary GH content, and abolished the GH rise due to acute admin istration of GHRH. Coadministration of GHRH (20 ng/ 100 g body weight b.i.d., s.c. for 5 days) reestablished the ability of GHRH to elicit GH release in GH-treated pups [29]. The relevance of these findings for the GH therapy of nonclassically GH-deficient short children [30,31] whose GHRH-secreting structures are still preserved [32] does not escape attention (see also below).…”

Is Tryptophan ‘more’ Essential than Other Essential Aminoacids in Development? A Morphologic Study

“…Experimental observations (Cella et al., 1990; MacGregor and Leng, 2005) demonstrate that hypothalamic–serotoninergic activity is directly related to GH secretion in the rat, and that serotoninergic pathways participate in GH negative feed‐back effects in hypothalamus. Therefore a possibility to explain the fall of blood concentrations of GH in TF‐rats, can be found in the fact that serotoninergic neuronal pathways, that seem to play an essential role in control of pituitary hormone secretion (or release?…”