Dehydroepiandrosterone treatment attenuates oestrogen-induced pituitary hyperplasia

Abstract

The physiological importance of and therapeutic interest in dehydroepiandrosterone (DHEA) has been predominantly in relation to its action as an inhibitor of the promotion and progression of several kinds of tumours, including those of breast, prostate, lung, colon, liver and skin tissues. The aim of the present study was to determine the role of DHEA in diethylstilboestrol (DES)-induced pituitary hyperplasia. Female Sprague-Dawley rats were divided into four treatment groups: DES (implanted s.c. with a 20 mg DES pellet), DHEA (two 50 mg DHEA pellets), DHEA/DES (both DHEA and DES pellets), and controls (not implanted). Every week, all rats were weighed and cycled, and jugular blood samples were obtained. After 7 weeks, rats were killed. Hypophyses were removed and weighed, and serum prolactin, GH, IGF-I and leptin levels were assayed by RIA. DHEA cotreatment reduced pituitary enlargement by 39% in DES-treated rats. It also reduced the hyperprolactinaemia (280·4 43·6 ng/ml for DHEA/DES vs 823·5 127·1 ng/ml for DES) and partially reversed the loss of body weight induced by DES. DHEA treatment did not modify the effects of DES on serum GH, IGF-I and leptin levels. But DHEA per se also increased pituitary weight and induced hyperprolactinaemia, although to a lesser degree than DES. We conclude that DHEA administration has beneficial effects on oestrogen-induced pituitary hyperplasia and hyperprolactinaemia, but the fact that DHEA per se also induces diverse hormonal effects and a slight pituitary enlargement limits its use as a possible therapeutic drug.

Dehydroepiandrosterone (DHEA) modulates GHRH, somatostatin and angiotensin II action at the pituitary level

“…On the other hand, DHEA pretreatment reduced the inhibitory action of somatostatin on GH, and not on prolactin, secretion. These results could be related to the DHEAinduced reversal of the inhibitory effect of ether stress on GH secretion, which we have previously described (Suárez et al 2002). From our results, it can be inferred that DHEA may release GH in vivo by reducing somatotrope responsiveness to somatostatin, as well as by enhancing somatotrope sensitivity to GHRH.…”

“…In a previous work we showed that in pituitary hyperplasia induced by estrogen in female rats, DHEA had several endocrine and metabolic effects, which depended mainly on the endocrine environment (Suárez et al 2002). We found that DHEA enhanced serum prolactin in rats in diestrus, though it partially reversed estrogen-induced hyperprolactinemia.…”

“…In experiments in rats in vivo we had observed that DHEA increased serum GH levels (Suárez et al 2002). Furthermore, it has also been reported that serum DHEA levels correlate positively with GH and IGF-I levels in nonobese women with functional hyperandrogenism (Legan et al 2002), in pubertal development, and in aging (Shealy 1995, Kroboth et al 1999.…”

“…The rat has proved to be an useful model to study the mechanism of action of DHEA. In a previous work we showed that this steroid attenuates estrogen-induced pituitary hyperplasia and hyperprolactinemia (Suárez et al 2002). Besides, DHEA per se produced diverse hormonal effects, such as serum prolactin and GH increase in vivo, which would restrict the clinical application of this drug in humans.…”

Characterization of Pituitary Cell Populations in Rats with Induced Polycystic Ovaries

“…This could be due to changes in the proliferation/apoptosis balance or to a hyperplasia or hypertrophy. In this sense, chronic administration of estrogen or long-acting estrogenic hormone preparations is known to produce this effect [Díaz-Torga et al, 1998;Suárez et al, 2002]. Although several studies have described gonadotrophin abnormalities in PCOS, the mechanism underlying the altered LH/FSH ratio has remained unclear.…”