Growth induced by pulsatile infusion of an amidated fragment of human growth hormone releasing factor in normal and GHRF-deficient rats

Abstract

The discovery of human pancreatic growth hormone releasing factors (GHRFs)^1,2 and subsequent characterization of human hypothalamic GHRF³ has led to studies on the role of these peptides in stimulating growth hormone (GH) release^4–6, and attempts to use GHRF peptides to increase growth rates in short children are already underway⁷. However, there is no experimental evidence in animals that exogenous GHRF promotes growth in vivo. Although anaesthetized rats release GH reproducibly in response to GHRF injections^4,8, the responses in conscious male rats are much more variable^5,6, perhaps because of their highly episodic endogenous GH secretory pattern⁹. In contrast, female rats secrete GH in a more continuous pattern¹⁰ and respond reproducibly to repeated injections of GHRF. We report here that it is possible to establish a ‘male’ type of GH secretory pattern in normal female rats by long-term pulsatile intravenous (i.v.) infusions of the active human GHRF fragment GHRF (1–29)NH₂. We found that this treatment accelerates growth and increases pituitary GH content, whereas continuous infusions of this GHRF fragment at the same daily dose are ineffective. Pulsatile, but not continuous GHRF also stimulates growth in animals made GHRF-deficient by neonatal monosodium glutamate treatment. Thus exogenous GHRF will stimulate growth in both GHRF-deficient and normal animals provided it is administered in an appropriate pattern.