The regulation of GH secretion by sex steroids.

Gonadal sex steroids modulate GH synthesis and secretion with effects on both the hypothalamus and anterior pituitary. In the post-pubertal animal, androgens and oestrogens modulate hypothalamic somatostatin (SS) and GHRH synthesis respectively. These effects may be direct as SS neurons express the androgen receptor and many GHRH neurons are oestrogen receptor positive. The neonatal steroid environment modulates the number of GHRH neurons in the adult hypothalamus, as well as their responsivity to post-pubertal steroids. Furthermore, both neonatal and post-pubertal steroids modulate hypothalamic synaptic organisation affecting the number of synaptic inputs and the morphology of glial cells. This in turn has important effects on the ability of the hypothalamus to drive the secretory pulsatility of anterior pituitary hormone release. At the level of the somatotroph, androgens and oestrogens have been reported to stimulate, inhibit or have no effect on GH synthesis. In primary cultures, we found no effect of either androgens or oestrogens on GH mRNA levels. However, the sex steroid environment significantly modified the response of somatotrophs to SS. Furthermore, males have more somatotrophs compared with female rats and this partially depends on the neonatal sex steroid environment. In conclusion, sex steroids have both organisational and activational effects on the GH axis. These effects range from modulating the number of hypothalamic neurons controlling GH secretion, their responsiveness to later steroids, and the synaptic connectivity and neuropeptide production, to modulation of somatotroph numbers in the anterior pituitary and their responsiveness to inputs controlling GH synthesis and secretion.