Endocrine Abstracts

The classical paradigm of lactotroph prolactin production and release is based around tonic inhibition by hypothalamic dopamine and stimulation by factors such as estrogen. We have recently shown that conditional ablation of pituitary androgen receptor (Foxg1-Cre ARKO) surprisingly does not change the concentration of circulating gonadotrophins but increases circulating prolactin in male mice; highlighting androgen signalling as a novel negative regulator of prolactin production. We aimed to refine our knowledge of the site and mechanism of action of this control by performing further genetic, pharmacological and surgical experiments to ablate the production and/or action of prolactin and/or androgens. Male mice with a genetic ablation of AR in neurons (Nestin-Cre ARKO) do not have an increase in circulating prolactin, confirming that the increase in prolactin seen in the Foxg1-Cre ARKO mouse is not due to loss of hypothalamic AR, but specifically pituitary AR. However, Foxg1-Cre ARKO mice treated with the dopamine agonist bromocriptine show a decrease in circulating prolactin levels suggesting that the mechanism of prolactin increase originates with the hypothalamic dopamine system that normally controls prolactin. Male mice with postnatal AR ablation in ~50% lactotrophs (Prolactin-Cre ARKO) do not show an increase in circulating prolactin, suggesting that either the mechanism is not lactotroph-specific or that ablation of AR needs to occur earlier or in a greater number of lactotrophs to result in an increase in circulating prolactin. Mice castrated in adulthood do not show an increase in circulating prolactin which suggests that the control mechanism is not an acute response to changes in androgens but is programmed during the pre-adult development of the pituitary. Further experiments are currently being undertaken to ablate AR in other pituitary cell populations and at earlier time points with the aim of pinpointing the spatio-temporal mechanism of control of prolactin production by androgen receptor signalling.