No evidence for prolactin’s involvement in the post-ejaculatory refractory period

In many species, ejaculation is followed by a state of decreased sexual activity, the post-ejaculatory refractory period. Several lines of evidence have suggested prolactin, a pituitary hormone released around the time of ejaculation in humans and other animals, to be a decisive player in the establishment of the refractory period. However, data supporting this hypothesis is controversial. We took advantage of two different strains of house mouse, a wild derived and a classical laboratory strain that differ substantially in their sexual performance, to investigate prolactin’s involvement in sexual activity and the refractory period. First, we show that there is prolactin release during sexual behavior in male mice. Second, using a pharmacological approach, we show that acute manipulations of prolactin levels, either mimicking the natural release during sexual behavior or inhibiting its occurrence, do not affect sexual activity or shorten the refractory period, respectively. Therefore, we show compelling evidence refuting the idea that prolactin released during copulation is involved in the establishment of the refractory period, a long-standing hypothesis in the field of behavioral endocrinology.

No evidence for prolactin’s involvement in the post-ejaculatory refractory period

In many species, ejaculation is followed by a state of decreased sexual motivation, the post-ejaculatory refractory period. Several lines of evidence have suggested prolactin, a pituitary hormone released around the time of ejaculation in humans and other animals, to be a decisive player in the establishment of the refractory period. However, data supporting this hypothesis is controversial. We took advantage of two different strains of house mouse, a wild derived and a classical laboratory strain, that differ substantially in their sexual behavior, to investigate prolactin’s involvement in sexual motivation and the refractory period. First, we show that there is prolactin release during sexual behavior in male mice. Second, using a pharmacological approach, we show that acute manipulations of prolactin levels, either mimicking the natural release during sexual behavior or inhibiting its occurrence, do not affect sexual motivation or shorten the refractory period, respectively. Therefore, we show compelling evidence refuting the idea that prolactin released during copulation is involved in the establishment of the refractory period, a long-standing hypothesis in the field of behavioral endocrinology.

Hyperprolactinemia in a male pituitary androgen receptor knockout mouse model is associated with a female-like pattern of lactotroph development

Circulating prolactin concentration in rodents and humans is sexually dimorphic. Estrogens are a well-characterised stimulator of prolactin release. Circulating prolactin fluctuates throughout the menstrual/estrous cycle of females in response to estrogen levels, but remains continually low in males. We have previously identified androgens as an inhibitor of prolactin release through characterisation of males of a mouse line with a conditional pituitary androgen receptor knockout (PARKO) which have an increase in circulating prolactin, but unchanged lactotroph number. In the present study we aimed to specify the cell type that androgens act on to repress prolactin release. We examined lactotroph-specific, Pit1 lineage-specific and neural-specific conditional AR knockouts, however they did not duplicate the high circulating prolactin seen in the pituitary androgen receptor knockout line, suggesting that the site of androgen repression of prolactin production was another cell type. Using electron microscopy to examine ultrastructure we showed that pituitary androgen receptor knockout male mice develop lactotrophs that resemble those seen in female mice, and that this is likely to contribute to the increase in circulating prolactin. When castrated, pituitary androgen receptor knockout males have significantly reduced circulating prolactin compared to intact males, which suggests that removal of circulating estrogens as well as androgens reduces the stimulation of pituitary prolactin release. However, when expression of selected estrogen-regulated anterior pituitary genes were examined there were no differences in expression level between controls and knockouts. Further investigation is needed into prolactin regulation by changes in androgen-estrogen balance, which has implications not only in the normal sexual dimorphism of physiology but also in diseases such as hyperprolactinemia.