Developmental programming: prenatal androgen exposure alters the gonadotroph population of the ovine pituitary gland

In utero exposure of the female foetus to androgens during development disrupts the reproductive axis and results in hypersecretion of luteinising hormone (LH) (but not follicle-stimulating hormone) in postnatal life. Abnormalities in the neural circuits controlling hypothalamic gonadotrophin-releasing hormone have been documented; however, androgens could also programme abnormalities in the pituitary gland. Ovine foetuses were exposed to either testosterone propionate or the non-aromatisable androgen dihydro-testosterone from days 30-90 of gestation (term 147 days) and the effects on the functional morphology of the pituitary were determined. Exogenous testosterone propionate exposure resulted in pituitary glands in adult male and female sheep that were 40% heavier than controls. Because this effect was not observed in the dihydro-testosterone-exposed animals, these actions are mediated via the oestrogen receptor (ER). No significant differences were apparent in 90- or 140-day foetuses. There was no difference between control and androgen-exposed animals in the density of LHβ or ERα immunoreactive cells in the pituitary although the density of follicle-stimulating hormone-β immunoreactive cells was lower in the testosterone-treated animals. The percentage of cells co-localising LHβ and ERα was lower in the testosterone-treated ewes and this may, in part, explain a reduced ability to respond to steroid feedback. Thus, enlargement of the pituitary gland, coupled with a reduced sensitivity to oestrogen negative-feedback, may contribute to the hyper-secretion of LH observed in animals that have been exposed to excess androgens during foetal life.