Growth hormone and reproduction in the female rat: a central role for somatostatin

It is well known that the somatotropic and gonadotropic axes are closely related: Both underproduction and overproduction of growth hormone (GH) affect reproduction. During aging, the decline in GH release and reproductive function appear to occur concurrently. Data from the literature suggest that somatostatin (SOM), the inhibiting factor in the bimodal hypothalamic regulation of GH release, is not only crucial for GH release patterns, but may also affect reproductive function. The aim of this thesis was to test the hypothesis that SOM neurons in the periventricular nucleus (PeVN) may play a central role in the interaction between both axes in the female rat.GH release patterns are sexually dimorphic, which has been suggested to result mainly from differences in SOM release from the median eminence (ME). Our data support the notion that the hypothalamic SOM system differs between the sexes. The PeVN in female rats likely possesses more SOM cells, but synthesis and, possibly, storage of SOM peptide may be higher in males. Also, the acute GH feedback on SOM cells, as monitored by the presence of a cFos-positive nucleus, is different between the sexes and, moreover, occurs in different subregions of the PeVN in male and female rats. Gonadal steroids may be involved in the regulation of hypothalamic GH feedback in the female, as we found that estrogen decreases the sensitivity of SOM cells to GH. Our findings suggest that the organization of SOM cells in the PeVN differs between the sexes, which may direct the proposed different SOM release patterns from the ME.In this thesis we show that SOM decreases the estrogen-induced luteinizing hormone (LH) surge in the female rat by, at least in part, decreasing hypothalamic GnRH cell activation. These data suggest that SOM may indeed directly affect reproductive function at the level of the hypothalamus and, possibly, the pituitary. Also, our data indicate that SOM neurons in the PeVN are regulated by both estrogen and progesterone, of which plasma levels increase during the day of proestrus. Hence, our data, combined with data from the literature, suggest that hypothalamic SOM neurons may be involved in the regulation of the proestrous LH surge in the female rat. Based on our results, we suggest that in the normal female cycle, SOM may be involved in the descending phase of the LH surge.Interestingly, in female rats of 9 months old that already showed an attenuated proestrous LH surge, we found changes in SOM peptide concentrations within the PeVN compared to young animals. The decline in GH release with age is suggested to result from increased SOM secretion from the ME. Our findings suggest that early aging of the somatotropic axis may be correlated with changes in the hypothalamic SOM system. Thus, early reproductive aging and age-related changes in the somatotropic axis occur simultaneously in the female rat, suggesting that SOM may also be involved in the age-related changes in reproductive function.In conclusion, we show that changes in GH release patterns (e.g. between the sexes or with age) are associated with altered activity of the PeVN SOM cells. These findings support our notion of the proposed central role of the hypothalamic SOM system in the interaction of the somatotropic axis with the reproductive system. Therefore, PeVN SOM neurons may indeed provide the "cross-link" between the functionality of the somatotropic and gonadotropic axis.