Hypothalamic Monoaminergic Activity and Pituitary Function in Male Rats with Estrogen-Induced Pituitary Hyperplasia

Abstract

The mechanism by which estrogen enhances prolactin (PRL) secretion and induces hyperplasia of lactotrophs is not defined clearly. The objective of this study was to examine hypothalamic monoaminergic PRL regulatory systems and pituitary hormone secretion in the early and later stages of estrogen-induced hyperprolactinemia and pituitary hyperplasia. Dopamine (DA) and serotonin (5-HT) turnover were determined in microdissected brain regions 3 and 30 days after a single subcutaneous dose of estradiol (2 mg) to male ACI rats. Plasma samples were collected in animals with indwelling intra-atrial cannulae. 3 days after estrogen there was a significant increase in plasma PRL, pituitary PRL and growth hormone (GH), and DA turnover in the median eminence and arcuate nucleus. Plasma concentrations and pituitary content of PRL increased at 30 days. The responsiveness of PRL to thyrotropin-releasing hormone (TRH) was enhanced at both times. Concentrations of DA decreased considerably in the median eminence and arcuate nucleus by 30 days, and turnover decreased in the median eminence. 5-HT turnover was not affected in the early stages of hyperprolactinemia. Plasma GH increased and TSH was unchanged, even though pituitary content of both hormones decreased at 30 days. Estrogen had no effect on plasma corticosterone. These findings support the hypothesis that estrogen induces pituitary hyperplasia by antagonizing DA inhibition of PRL-secreting cells and by enhancing their responsiveness to TRH.

Effects of estradiol on aldosterone secretion in ovariectomized rats

“…This result is in agreement with previous studies that estrogen stimulates PRL release, both in vivo [Terry et al, 1985] and in vitro [Ben-David et al, 1964;Nicoll and Meites, 1964]. The role of PRL in adrenal function and steroid hormone secretion has been studied.…”

Effects of estradiol on corticosterone secretion in ovariectomized rats

“…We confirmed that in vivo treatment with EB in Ovx rats resulted in a dose-dependent increase the secretion of plasma PRL compared to oiltreated Ovx rats. This is consistent with the observation that acute and chronic effects of E 2 on male rats yield a significant increase in plasma PRL and pituitary PRL [Terry et al, 1985]. However, these results indicate that there is positive correlation between plasma PRL and corticosterone under the influence of E 2 .…”

“…It has been well-established that the effects of estrogen on plasma and pituitary PRL could be a direct action of estrogen on pituitary lactotrophs [Terry et al, 1985] or due to indirect effects of estrogen on hypothalamic PRL regulatory systems, i.e., inhibition of dopamine release [Casanueva et al, 1982] or stimulation of serotonin [Nakagawa et al, 1980]. We confirmed that in vivo treatment with EB in Ovx rats resulted in a dose-dependent increase the secretion of plasma PRL compared to oiltreated Ovx rats.…”

Responses to prolactin secretagogues in oestrogen-treated rats suggest that the defect in prolactin regulation produced by oestrogen is at the level of the pituitary gland

“…In a recent study, which examined the activity of dopamine neurones during the development of adenoma formation, it was shown that dopamine neurones continue to function actively even while oestrogen levels are high (Terry, Craig, Hughes et al 1984). The purpose of the present study was to charac¬ terize prolactin regulation during the acute develop¬ ment of oestrogen-induced pituitary hyperplasia with a pharmacological approach, testing for potential pituitary and hypothalamic disturbances.…”