Dose-dependent effects of 17-ß-estradiol on pituitary thyrotropin content and secretion in vitro

Abstract

We studied the basal and thyrotropin-releasing hormone (TRH) (50 nM) induced thyrotropin (TSH) release in isolated hemipituitaries of ovariectomized rats treated with near-physiological or high doses of 17-ß-estradiol benzoate (EB; sc, daily for 10 days) or with vehicle (untreated control rats, OVX). One group was sham-operated (normal control). The anterior pituitary glands were incubated in Krebs-Ringer bicarbonate medium, pH 7.4, at 37 o C in an atmosphere of 95% O 2 /5% CO 2 . Medium and pituitary TSH was measured by specific RIA (NIDDK-RP-3). Ovariectomy induced a decrease (P<0.05) in basal TSH release (normal control = 44.1 ± 7.2; OVX = 14.7 ± 3.0 ng/ml) and tended to reduce TRH-stimulated TSH release (normal control = 33.0 ± 8.1; OVX = 16.6 ± 2.4 ng/ml). The lowest dose of EB (0.7 µg/ 100 g body weight) did not reverse this alteration, but markedly increased the pituitary TSH content (0.6 ± 0.06 µg/hemipituitary; P<0.05) above that of OVX (0.4 ± 0.03 µg/hemipituitary) and normal rats (0.46 ± 0.03 µg/hemipituitary). The intermediate EB dose (1.4 µg/ 100 g body weight) induced a nonsignificant tendency to a higher TSH response to TRH compared to OVX and a lower response compared to normal rats. Conversely, in the rats treated with the highest dose (14 µg/100 g body weight), serum 17-ß-estradiol was 17 times higher than normal, and the basal and TRH-stimulated TSH release, as well as the pituitary TSH content, was significantly (P<0.05) reduced compared to normal rats and tended to be even lower than the values observed for the vehicle-treated OVX group, suggesting an inhibitory effect of hyperestrogenism. In conclusion, while reinforcing the concept of a positive physiological regulatory role of estradiol on the TSH response to TRH and on the pituitary stores of the hormone, the present results suggest an inhibitory effect of high levels of estrogen on these responses.

Ovarian steroids influence cell proliferation in the dentate gyrus of the adult female rat in a dose‐ and time‐dependent manner

“…This is generally in agreement with other reports that estrogen is capable of altering numerous physiological and behavioral measures at low to moderate, but not relatively high, doses of hormone (DiazVeliz et al, 1991;Moreira et al, 1997;Rusa et al, 1999). Although the mechanisms underlying such dosedependent effects of estrogen have yet to be fully elucidated, these phenomena are likely to be, at least in part, due to ER down-regulation (Medlock et al, 1991a,b;Lauber et al, 1991a).…”

Effect of medroxyprogesterone acetate on thyrotropin secretion in adult and old female rats

“…The in vitro assay also showed a stimulatory effect of MPA treatment on basal and TRH-induced TSH release from the pituitaries of adult OVX rats. We (14) and others (3,15,16) had shown that the decreased TSH response to TRH of OVX rats was restored by estrogen treatment. We also had reported before (5) a stimulatory effect of testosterone given chronically to castrated male rats on in vitro basal and TRH-stimulated TSH release.…”

Estrogen potentiates adrenocortical responses to stress in female rats

“…On the other hand, earlier studies used either supraphysiological doses of E 2 (ϳ500 pg/ml) (60) or longer E 2 exposure time (21 days) (3). It should be noted that the physiological effects of E 2 are particularly sensitive to specific experimental paradigms (2,11,23,39,53,61), and it is very likely that the discrepancy among these studies arises from differences in steroid dosage and exposure time. Importantly, despite the fact that E 2 effects can be sensitive to the replacement protocol, the present work shows consistent HPA axis effects using two different E 2 replacement methods.…”