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

Steroid hormones have been implicated in the modulation of TSH secretion; however, there are few and controversial data regarding the effect of progesterone (Pg) on TSH secretion. Medroxyprogesterone acetate (MPA) is a synthetic alpha-hydroxyprogesterone analog that has been extensively employed in therapeutics for its Pg-like actions, but that also has some glucocorticoid and androgen activity. Both hormones have been shown to interfere with TSH secretion. The objective of the present study was to investigate the effects of MPA or Pg administration to ovariectomized (OVX) rats on in vivo and in vitro TSH release and pituitary TSH content. The treatment of adult OVX rats with MPA (0.25 mg/100 g body weight, sc, daily for 9 days) induced a significant (P<0.05) increase in the pituitary TSH content, which was not observed when the same treatment was used with a 10 times higher MPA dose or with Pg doses similar to those of MPA. Serum TSH was similar for all groups. MPA administered to OVX rats at the lower dose also had a stimulatory effect on the in vitro basal and TRH-induced TSH release. The in vitro basal and TRH-stimulated TSH release was not significantly affected by Pg treatment. Conversely, MPA had no effect on old OVX rats. However, in these old rats, ovariectomy alone significantly reduced (P<0.05) basal and TRH-stimulated TSH release in vitro, as well as pituitary TSH content. The results suggest that in adult, but not in old OVX rats, MPA but not Pg has a stimulatory effect on TSH stores and on the response to TRH in vitro

Effects of estradiol benzoate on 5'-iodothyronine deiodinase activities in female rat anterior pituitary gland, liver and thyroid gland

There is little information on the possible effects of estrogen on the activity of 5'-deiodinase (5'-ID), an enzyme responsible for the generation of T3, the biologically active thyroid hormone. In the present study, anterior pituitary sonicates or hepatic and thyroid microsomes from ovariectomized (OVX) rats treated or not with estradiol benzoate (EB, 0.7 or 14 mug/100 g body weight, sc, for 10 days) were assayed for type I 5'-ID (5'-ID-I) and type II 5'-ID (5'-ID-II, only in pituitary) activities. The 5'-ID activity was evaluated by the release of (125)I from deiodinated (125)I rT3, using specific assay conditions for type I or type II. Serum TSH and free T3 and free T4 were measured by radioimmunoassay. OVX alone induced a reduction in pituitary 5'-ID-I (control = 723.7 + 67.9 vs OVX = 413.9 + 26.9; P<0.05), while the EB-treated OVX group showed activity similar to that of the normal group. Thyroid 5'-ID-I showed the same pattern of changes, but these changes were not statistically significant. Pituitary and hepatic 5'-ID-II did not show major alterations. The treatment with the higher EB dose (14 mug), contrary to the results obtained with the lower dose, had no effect on the reduced pituitary 5'-ID-I of OVX rats. However, it induced an imporatnt increment of 5'-ID-I in the thyroid gland (0.8 times higher than that of the normal group: control = 131.9 + 23.7 vs OVX + EB 14 mug = 248.0 + 31.2; P<0.05), which is associated with increased serum TSH (0.6-fold vs OVX, P<0.05) but normal serum free T3 and free T4. The data suggest that estrogen is a physiological stimulator of anterior pituitary 5'-ID-I and a potent stimulator of the thyroid enzyme when employed at high doses.

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

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-Beta-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 C in an atmosphere of 95 percent O2/5 percent CO2. 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 tendend 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 mug/100 g body weight) did not reverse this alteration, but markedly increased the pituitary TSH content (0.6 + 0.06 mug/hemipituitary; P<0.05) above that of OVX (0.4 + 0.03 mug/hemipituitary) and normal rats (0.46 + 0.03 mug/hemipituitary). The intermediate EB dose (1.4 mug/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 mug/100 g body weight), serum 17-Beta-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.

Acute effect of thyroxine on pituitary neuromedin B content of hypothyroid rats and its correlation with TSH secretion

Neuromedin B (NB) is a bombesin-like peptide that has been recently characterized as a physiological paracrine/autocrine inhibitor of thyrotropin (TSH) secretion. We report here the time course of the effect of thyroxine (T4) administration to hypothyroid rats on the anterior pituitary content of NB. Dutch-Miranda male rats weighing 250-300 g received 0.03 percent methimazole in the drinking water for 3 weeks. T4(0.8µg/100 g body weigh, sc) was given 1/2, 1,2 or 6 h before sacrifice. One group recived saline rather than T4 (hypothyroid control). The groups contained 6 to 8 animals each. NB, extracted from tissue by boiling in acetic acid, was measured by radioimmunoassay, using a highly specific anti-serum. Pituitary NB content was significantly increased 4-fold, as ealry 1/2 h after T4 injection, while serum TSH level was similar to that of the hypophyroid control group. The peak response to T4 was at 4 h after injection, when NB content was increased 8-fold (hypothyroid: 45 ñ 8; 1/2h, 223 ñ 15; 1h, 203 ñ 48; 3h, 383 ñ 31; 6h, 224 ñ 30 fmol/mg protein) and serum TSH decreased to the level of normal rats (0.93-1.5 ng/ml) generally observed in our laboratory (jypothyroid: 31 ñ 3; 1/2h, 26 ñ 3; 1h, 31 ñ 2; 3h, 1.3 ñ 0.1; 6h, 3.7 ñ 0.6 ng/ml). These data suggest that NB synthesis is rapidly induced by thyroxine and this might represent a new regulatory pathy involved in the acute inhibitory effect of thyroid hormones on TSH secretion

Paradoxical effect of neuromedin B and thyroxin on thyrotropin secretion from isolated hyperthyroid pituitaries

Neuromedin B (NB) is a bombesin-like peptide that we recently characterized as a physiological autocrine inhibitor of thyrotropin (TSH) secretion. We now report the effect of NB, thyroxin (T4) and NB + thyroxin on basal and THR (50 nM)-stimulated TSH release from isolated hemipituitaries of hyperthyroid rats. To induce hyperthyroidism, 20 rats were treated with 0.03 per cent methimazole for one month and then received T4, 4 micrograms/100 g body weight, sc, daily for 7 days. Each experimental group consisted of 7 to 9 hemipituitaries. TSH was measured using a rat TSH kit provided by NIDDK. Basal TSH release was paradoxically increased in the presence of 0.1 microM T4 or 0.1 microM NB and even two times higher in the presence of both (Control: 30.0 +/- 4.2 ng/ml; T4: 58.6 +/- 5.6 ng/ml; NB: 53.4 +/- 6.1 ng/ml; T4 + NB: 90.4 +/- 8.5 ng/ml). The percent increment above basal TSH levels after TRH was higher only in the presence of NB (Control: 44.5 +/- 8.2 per cent , NB: 105.3 +/- 18.8 per cent ; P < 0.05). Altered responsiveness in hyperthyroidism and direct modification of the intracellular metabolism of T4 are mechanisms that could explain this paradoxical effect