Sexually Dimorphic Expression of sst1 and sst2 Somatostatin Receptor Subtypes in the Arcuate Nucleus and Anterior Pituitary of Adults Rats

Abstract

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.

Somatostatin and its receptors contribute in a tissue-specific manner to the sex-dependent metabolic (fed/fasting) control of growth hormone axis in mice

“…These results are consistent with reports on rats (24,72) showing that the female PIT expresses less sst2 and sst5 compared with male PIT. Although the majority of sst subtypes were lower in the female PIT, the expression of sst1 was greater compared with males, as reported previously by others (55) but not observed by all (72). It remains to be determined what factors are responsible for these sex-dependent differences in SST/sst expression in the PIT.…”

“…In fact, cell-specific regulation of SST expression is supported by the observation of some (11,20,28,41,42) but not all authors (5,26) showing that female rats and mice have lower immunodetectable SST in specific hypothalamic regions (i.e., median eminence, periventricular nucleus) compared with males, where these changes are associated with a reduction in SST mRNA levels in the periventricular nucleus but not in the arcuate nucleus. Also, Zhang et al (72) observed that sst1 mRNA-expressing cells were two-to threefold greater in the arcuate, but not in the ventromedial, nucleus of the HPT in males compared with female rats. Thus, future (neuro)anatomic studies in these animal models may help to unequivocally ascertain this apparent lack of sex-related differences in SST/ssts at the HPT and stomach levels.…”

Subcellular Dynamics of Somatostatin Receptor Subtype 1 in the Rat Arcuate Nucleus: Receptor Localization and Synaptic Connectivity Vary in Parallel with the Ultradian Rhythm of Growth Hormone Secretion

“…ARC GHRH neurons express high levels of sst 1 and sst 2A mRNA . Both receptor proteins are present in the ARC, whereas other SRIF receptor subtypes are of low abundance in this area (Hervieu and Emson, 1998;Stroh et al, 2006;Kumar, 2007) (but see also Helboe et al, 1998), consistent with the involvement of sst 1 and sst 2 in the hypothalamic regulation of GH secretion (Guo et al, 1996;Zheng et al, 1997;Zhang et al, 1999;Lanneau et al, 2000).…”

Somatostatin is required for masculinization of growth hormone–regulated hepatic gene expression but not of somatic growth

“…Semiquantitative RT-PCR was used to determine whether SST and SSTR1-5 exhibited baseline sexual diergism in the mouse as reported previously for SSTR1 and 2 in rat (11), and whether the complete absence of SST would alter expression of the structurally related peptide CST or SSTRs in a sex-dependent pattern. There was a clear sexual diergism in SST gene expression in wild-type hypothalamus and pituitary gland; male mice had SST mRNA levels more than twofold those of female mice in both tissues, and no expression was detected in the Smst -/-mice (Table 1).…”

“…Furthermore, sexual diergism has been noted for expression of SSTR1, 2, 3, and 5 in the anterior pituitary and for SSTR1 but not SSTR2 in the rat hypothalamus (11)(12)(13). Although estrogen and testosterone both influence hypothalamic Smst gene expression and play a major developmental role in organizing the sexual diergism of GH secretion, the effect of gonadal steroids is not limited to the critical perinatal period of imprinting.…”