Single exposure to testosterone in adulthood rapidly induces regularity in the growth hormone release process

The neonatal gonadal steroid milieu is known to be important in imprinting the striking sexual dimorphism of growth hormone (GH) secretion; however, the influence of the sex steroids on GH control in adult life and their mechanism/site of action are largely unknown. In the present study, we tested the hypothesis that testosterone (T) subserves the gender-specific regularity of the GH release process in adulthood. The approximate entropy statistic (ApEn) was used to quantify the degree of regularity of GH release patterns over time. Eighteen hours after a single subcutaneous injection of 1 mg T, both sham-operated and ovariectomized (OVX) female adult rats displayed plasma GH profiles that were strikingly similar to the regular male-like ultradian rhythm of GH secretion. The highest ApEn values, denoting greater disorderliness of GH secretion, were observed in the ovary-intact group, and T injection significantly (P < 0.001) reduced this irregularity whether or not the ovaries were present. Serial intravenous injections of GH-releasing hormone (GHRH) caused a similar increase in plasma GH levels in sham-operated females independently of time of administration. In contrast, female rats administered T exhibited a male-like intermittent pattern of GH responsiveness to GHRH, the latter known to be due to the cyclic release of endogenous somatostatin. These results demonstrate that acute exposure to T during adult life can rapidly and profoundly "masculinize" GH pulse-generating circuits in the female rat. Our findings suggest that the enhanced orderliness characteristic of the GH release process in males, compared with females, is regulated by T. We postulate that this T-induced regularity is mediated at the level of the hypothalamus by inducing regularity in somatostatin secretion, which in turn governs overall GH periodicity.