The pattern of growth hormone (GH) secretion and rate of somatic growth are markedly sexually dimorphic, but the underlying neuroendocrine mechanisms are far from clear. In the present study, we tested the hypothesis that the sexual dimorphism of GH secretion may be due to gender-related differences in the transduction of somatostatin's actions in brain and/or pituitary. To accomplish this, we compared the distributional pattern and level of expression of two somatostatin receptor subtypes, sst1 and sst2, in the brain and pituitary of adult male and female rats by in-situ hybridization using 35S-labelled antisense riboprobes. In the brain, the hybridization pattern and labelling density of sst1 and sst2 mRNA-expressing cells, as revealed by computer-assisted image analysis, in areas including the cerebral cortex, medial habenula (MHb) and ventromedial hypothalamic nucleus (VMN), were similar in male and female rats. In contrast, there was a marked sex-related difference in sst1 expression in the arcuate nucleus of the hypothalamus; both the number and labelling density of sst1 mRNA-expressing cells were two- to threefold greater in males than in females and this significant increase was homogenous throughout the rostrocaudal extent of the nucleus. No gender-related differences in arcuate sst2 mRNA levels were found. At the level of the anterior pituitary, the labelling density of sst2 mRNA in males was significantly higher than that of females. No sex-related difference in pituitary sst1 mRNA was observed. These results demonstrate a sexual dimorphism in the expression of two somatostatin receptor subtypes, sst1 and sst2, at the level of the arcuate nucleus and anterior pituitary, respectively. Such dimorphism suggests a differential involvement of sst1 and sst2 in GH regulation with respect to gender, and may imply roles for sst2 and sst1 in transducing somatostatin's actions on pituitary somatotrophs and GH-releasing hormone-containing arcuate neurones, respectively, to generate the lower basal and higher GH pulse levels characteristic of the male rat.

The secretion of growth hormone (GH) is governed by an intricate interplay between two hypothalamic hormones, the stimulatory GH-releasing hormone GHRH (1, 2), and its inhibitory counterpart somatostatin (SS) also known as GH-release inhibiting hormone (3). Their interaction generates a markedly pulsatile pattern of GH release in both man and experimental animals; the rat in particular exhibits a striking ultradian rhythm of GH secretion (4). This paper focuses on the physiological significance of SS and GHRH and their interrelationship in the genesis of the rhythmic secretion of GH. PHYSIOLOGICAL ROLES OF SS AND GHRH IN THE GENESIS OF THE GH RHYTHMThe role of endogenous SS in generating the ultradian rhythm of GH secretion has been investigated by several groups using the technique of passive immunization (5)(6)(7)(8). In general, these studies, conducted in a variety of species, demonstrated that immunoneutralization with anti-SS serum caused an augmentation of baseline GH but did not abolish the episodic bursts of GH release. These findings provide support for the concept that SS is a physiological regulator of GH trough levels and is probably released episodically into the hypophyseal portal circulation to inhibit GH release. Furthermore, the results suggest that the secretion of GH is regulated by the interaction of at least two hypothalamic hormones.Similar experiments carried out to investigate the role of GHRH on pulsatile GH secretion showed that administration of specific rat GHRH antisera almost totally abolished spontaneous GH surges (9-11). Thus there is strong evidence that the ultradian pulses of GH secretion are due to the episodic release of hypothalamic GHRH.While it is clear that SS and GHRH, individually, play crucial roles in GH regulation, very little is known about the nature of the SS/GHRH interaction, and how this interaction affects GH secretion. A series of studies has therefore been undertaken to investigate this interrelationship.In one of these studies (12), GH responsiveness to exogenous GHRH was found to be significantly greater at the time of a GH peak than during trough periods of the GH rhythm; neutralization of endogenous circulating SS eliminated this time-dependent difference. These data provided further support for the idea that hypothalamic SS release is increased episodically during trough periods, and led to the hypothesis that in the male rat, SS and GHRH are released rhythmically from the hypothalamus into the hypophyseal portal blood in 3-4 hour cycles, about 180" out of phase, thus generating the ultradian rhythm of GH secretion (Fig. 1). This hypothesis is strongly supported by the results of experiments by Plotsky and Vale (13), in which levels of immunoreactive GHRH and SS in rat hypophyseal portal blood were directly measured. The findings of Vance et al. (14) also support the concept that pulsatile GH secretion in man results from a combination of enhanced GHRH secretion with concomitant reduction of SS secretion. TEMPORAL PATTERN OF SS/GHRH SIGNALLING IN GH REG...