Reproduction Abstracts

Production of testosterone by testicular Leydig cells is under tight regulation by the hypothalamic – pituitary – gonadal (HPG) axis. GnRH, secreted by the hypothalamus, stimulates secretion of LH from the pituitary. LH will then stimulate testosterone production in the Leydig cells, which will feedback to the hypothalamic-pituitary element to inhibit LH secretion.

Previously it was accepted that testosterone exerted its negative feedback actions on the pituitary by binding to androgen receptor. However, several recent clinical and experimental studies have suggested that androgen-AR signalling in the pituitary may be redundant for the control of LH secretion, and that feedback may act via testosterone conversion to estradiol.

To investigate the possible role(s) of AR in the male pituitary, we have developed a unique transgenic mouse line where the androgen receptor is conditionally ablated in the pituitary (PARKO). Initial analysis demonstrated that LH transcript levels, as well as LH and testosterone circulating levels remain unchanged in PARKO males. Aromatase transcript was not found in the pituitaries of either control or PARKO males, however surprisingly both pituitary prolactin transcript and circulating prolactin were significantly increased.

Results suggest that inhibition of LH by testosteroneis not acting at the level of the pituitary in the mouse. If pituitary feedback is via estrogens, then production must be at a site other than the pituitary. In contrast these results suggest that a role of pituitary AR-signalling is to negatively regulate prolactin production, however further study is necessary to elucidate this mechanism.