To what extent is estrogen a qualitatively distinct trophic stimulus in the pituitary?

Physiological levels of circulating corticosterone and testosterone tonically inhibit mitotic activity in the pituitary. The wave of increased mitosis that results from withdrawal of either or both of these lasts for less than a week despite their continuing absence. In contrast, estrogen is a very powerful pituitary mitogen that at high dose is believed to exert a continuous trophic stimulus. To investigate this, we have carried out a careful analysis of the effects of 7 and 28 days estrogen treatment on anterior pituitary mitotic activity in ovariectomized 10 week-old Wistar rats using both bromodeoxyuridine (BrdU) and timed colchicine-induced mitotic arrest methodology. An estrogen dose-dependent increase in mitotic index was seen 7 days after the start of treatment as expected, representing an acceleration in gross mitotic rate from 1.7%/day in the absence of any estrogen replacement to 3.7%/day following the higher dose of estrogen treatment. Despite continued exposure to high dose estrogen and persistence of the increase in pituitary wet weight, the increase in mitotic index was unexpectedly not sustained. After 28 days of high dose estrogen treatment, anterior pituitary mitotic index and BrdU-labelling index were not significantly different from baseline. These data suggest that in keeping with other trophic stimuli to the pituitary, the mitotic response to longer-term high dose estrogen exposure is transient and is not the driver of persistent pituitary growth, at least in female Wistar rats.