The Interrelationship of Growth Hormone (GH)-Releasing Factor and Somatostatin in Generation of the Ultradian Rhythm of GH Secretion^*

TLDR

The study aimed to clarify how GH‑releasing factor (GRF) and somatostatin (SRIF) interact to generate the ultradian rhythm of GH secretion by testing human pancreas GRF‑44 and rat hypothalamic GRF with SRIF antiserum. Male rats were chronically cannulated and given 10 µg of either peptide intravenously at peak (1100 h) and trough (1300 h) times, after pretreatment with SRIF antiserum or normal sheep serum, and six‑hour GH profiles were recorded. SRIF antiserum abolished the peak‑trough difference in GH response, enabled marked GH release at trough, amplified peak responses, and revealed that rat GRF induced greater GH than human GRF, supporting a model of tonic GRF and SRIF secretion with rhythmic surges driving the ultradian GH rhythm. Endocrinology 115: 1952–1957, 1984.

Abstract

To further delineate the relationship between GH-releasing factor (GRF) and somatostatin (SRIF) in generation of the ultradian rhythm of GH secretion, we used two GRF peptides, human pancreas (hp) GRF-44 and rat hypothalamic (rh) GRF, and studied their interaction with SRIF by passive immunization with a specific antiserum (AS) to SRIF. Freely moving, chronically cannulated male rats were given 10 μg of either hpGRF-44 or rhGRF, iv, during peak (1100 h) and trough (1300 h) periods of the GH rhythm. Six-hour plasma GH profiles were obtained after pretreatment with either SRIF AS or normal sheep serum (NSS) as a control. In NSS-treated rats, the plasma GH responses to both hpGRF-44 and rhGRF were significantly greater when the peptides were administered during peak than during trough periods. Immunoneutralization with SRIF AS eliminated these differences and permitted marked GH release in response to both peptides at 1300 h. In addition, SRIF AS augmented the GRF-induced GH response at 1100 h compared with that in NSS controls. The rhGRF peptide caused significantly more GH release than hpGRF under both conditions. These results demonstrate that 1) the GH-releasing abilities of the GRF peptides vary markedly according to the time of injection; 2) the weak GRF-induced GH response observed during trough periods of the GH rhythm is due to antagonization by endogenous circulating SRIF; and 3) the rat-derived GRF may be a more potent GH secretagogue than the human-derived peptide in the rat. The findings reported here together with the available evidence provide support for the hypothesis that GRF and SRIF are secreted tonically from the hypothalamus into the hypophyseal portal blood, and that superimposed upon this steady state release is an additional 3- to 4-h rhythmic surge of each peptide, providing for integration of the ultradian rhythm of GH secretion, as observed in peripheral blood. (Endocrinology115: 1952–1957, 1984)