Sexual Differentiation of Growth Hormone Feedback Effects on Hypothalamic Growth Hormone-Releasing Hormone and Somatostatin

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Abstract
To investigate possible sex differences in the feedback regulation of growth hormone (GH) secretion, concentrations of immunoreactive GH-releasing hormone (GRF) and somatostatin (SS) were measured in the median eminence (ME) and the hypothalamus of male and female rats bearing the MtTWl 5 tumor, which secretes high amounts of GH and prolactin (PRL). Four weeks after tumor implantation in male rats, the GRF concentration in the whole hypothalamus, including the ME, was decreased by 37% (0.29 ± 0.02 vs. 0.46 ± 0.02 ng/mg protein in intact male controls; p < 0.001) and the concentration of SS was increased by 40% (11.5 ± 0.7 vs. 8.1 ± 0.3 ng/mg protein in male controls; p < 0.01). In female rats, the presence of tumor for 4 weeks caused a smaller (18%) reduction in GRF concentrations (0.27 ± 0.02 vs. 0.33 ± 0.03 ng/mg protein in intact female controls; p < 0.05) and no significant change in SS concentrations (10.2 ± 0.8 vs. 9.7 ± 0.8 ng/mg protein in female controls). Tumor-related changes in GRF and SS concentrations were also more pronounced in male rats than in females, when determined separately in the microdissected ME and in the remaining hypothalamus. These differences occurred despite similar increases in serum GH, PRL and insulin-like growth factor I concentrations in male and female tumor-bearing rats. To assess which hormone (GH or PRL) was responsible for these changes, intact male rats were treated for 10 days with 2 daily s.c. injections of rat GH (rGH; 100 and 250 µg/day), rat PRL (100 and 250 µg/day) or vehicle. Only the highest dose of rGH caused a significant (20%) reduction in ME GRF concentrations (p < 0.05). We conclude that while GH may exert a feedback control of its own secretion by decreasing GRF and increasing SS in the hypothalamus and the ME, these effects, however, are sexually differentiated, being significantly more pronounced in male rats than in females. These differences may contribute to the generation of the sex-specific GH secretory pattern.