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Biomedical subjects

G A Hedge

Publications and source records attributed to G A Hedge.

At least 55 records · Page 3Linked to original sources
PubMed1981

The effects of prostacyclin (PGI2) on prolactin secretion in vitro.

Continuously superfused rat anterior pituitary cells were used to study the effects of exogenous prostaglandins (PGs) and thromboxanes (TXs) on the secretion of prolactin (PRL). No change in hormone release was observed upon superfusion with TXB2 (10(-5)M) or the TX synthesis inhibitor, imidazole (1.5 mM). PGs A2, B2, D2, E1, E2, F1 alpha, F2 alpha, and endoperoxide analogs, U-44069 and U-46619, also had no effect on PRL secretion (all at 10(-5)M). In contrast 10(-5)M PGI2 was repeatedly found to stimulate PRL release to a level at least 125% above control, while producing no apparent change in the amount of hormone secreted in response to TRH. Somatostatin (SRIF), at a dose of 10(-6)M, maximally inhibited TRH-induced PRL output, but failed to alter the PRL response to PGI2. These studies indicate that PGI2 may have a direct effect on the anterior pituitary to modify PRL secretion.

Animals↗
PubMed1981

Corticosterone secretion after inhibition of prostaglandin synthesis by indomethacin.

Systemic indomethacin (Ind) administration decreased prostaglandin F (PGF) content of the rat adrenal to less than 1.4 pg/mg. This was less than 5% of the adrenal PGF content in the gelatin-treated (Gel) control group (34 pg/mg). Basal plasma corticosterone levels were increased by the Ind treatment. Since the calculated metabolic clearance rate for corticosterone was unchanged, this increase was attributed to an enhanced adrenal secretion rate that was secondary to elevated plasma ACTH concentration. Ether exposure in the presence of Ind did not stimulate a normal rise in plasma corticosterone or adrenal corticosteroidogenesis. Adrenal responsiveness to exogenous ACTH was reduced after Ind treatment. There was a normal rise in plasma ACTH levels following ether exposure confirming the adrenal as the site of inhibition. Systemic Ind treatment thus appears to have two sites of action in altering plasma corticosterone levels: 1) a direct effect on the adrenal, inhibiting normal secretion in response to acute elevations of plasma ACTH, and 2) an action at the pituitary or hypothalamic level, eliciting an increase in basal ACTH secretion.

Adrenal Cortex↗
PubMed1981

Feedback regulation of thyrotropin by thyroxine under physiological conditions.

We have studied the contribution of thyroxine (T4) itself to the feedback regulation of thyrotropin (TSH) secretion. Thyroidectomized rats received T4 replacement by one of two methods: 1) 5 or 10 micrograms T4 . 100 g-1 . day-1 in drinking water or 2) continuous subcutaneous infusion of 0.5, 1.0, or 2.0 micrograms T4 . 100 g-1 . day-1. Replacement of 5 micrograms T4 . 100 g-1 . day-1 resulted in elevated plasma T4 and TSH while triiodothyronine (T3) was decreased. Replacement of 10 micrograms T4 . 100 g-1 . day-1 resulted in greater elevation of plasma T4, a transient decrease in T3, and no change in plasma TSH. Continuous replacement of T4 resulted in a dose-dependent elevation of plasma T4, little plasma T3 generation, and inhibition of the postthyroidectomy rise in plasma TSH. The pituitary responsiveness to thyrotropin-releasing hormone (TRH) was increased in groups receiving 1.0 or 2.0 micrograms T4 . 100 g-1 . day-1. It was concluded that 1) the plasma T4 exerts a negative feedback on basal TSH secretion in addition to that due to plasma T3 and 2) small amounts of T4 replacement enhance the TSH response to exogenous TRH in short-term hypothyroid rats.

Animals↗
PubMed1981

Dynamics and regulation of TSH secretion by superfused anterior pituitary cells.

Superfused dispersed cells respond rapidly to 2- to 10-min pulses of TRH (10(-10) to 10(-7) M) in a dose-dependent manner. The effects of decreasing the stimulus duration can be overcome by a proportional increase in concentration of TRH. A TRH stimulus of 10 min or greater duration results in a sharp peak in TSH secretion followed by a lower plateau. Somatostatin (10(-8) M inhibits the response to TRH (t X 10(-9) M). T3 (2.0 microgram/dl) inhibits TRH-induced TSH secretion by superfused pituitary fragments, but not by dispersed cells. Corticosterone (50 microgram/dl), however, inhibits crude CRF-induced ACTH secretion by such cells.

Adrenal Glands↗
PubMed1981

Effect of continuous thyroxine administration on thyrotropin secretion in thyroidectomized rats.

We have studied the effect of T4 itself (i.e. without extrapituitary conversion to T3) on the feedback regulation of pituitary TSH secretion in thyroidectomized rats receiving continuous T4 or T3 replacement. Continuous sc infusion of 1.0 or 2.0 microgram T4/100 g . day in 0.01 N NaOH, 20% 1,2-propanediol vehicle failed to maintain the plasma T4 concentration in thyroidectomized rats for more than 48 h, despite the verification of T4 delivery. Continuous sc infusion of 1.0 or 2.0 microgram T4/100 g . day in 0.01 N NaOH, 5% rat serum resulted in a dose-dependent elevation in the plasma T4 concentration and inhibition of the postthyroidectomy rise in plasma TSH, in the presence of low plasma T3 concentrations. Mimicking the low plasma T3 concentrations that resulted from T4 infusion by continuous replacement of 280 ng T3/100 g . day failed to inhibit the postthyroidectomy rise in plasma TSH. The pituitary responsiveness to TRH (250 ng/100 g, iv) after 96 h of thyroid hormone infusion was significantly (P less than 0.05) inhibited only in the group receiving 2.0 microgram T4/100 g . day. These results indicate that the plasma T4, concentration in addition to that of plasma T3, conveys feedback information to the pituitary. With regard to pituitary TSH secretion, T4 acts as both a prohormone giving rise to a protion of the plasma T3 by peripheral monodeiodination and as a hormone conveying feedback information via the blood to the pituitary.

Animals↗
PubMed1981

Effects of various prostanoids on thyrotropin secretion by superfused anterior pituitary cells.

Continuously superfused rat anterior pituitary cells were used to study the effects of prostaglandins (PGs) and a thromboxane (TX) on the secretion of TSH. Indomethacin, a blocker of PG synthetase, inhibited the amount of TSH secreted in response to TRH. This reduction in TRH responsiveness was overcome by administration of PGE2 in combination with the TRH. Arachidonic acid, a prostanoid precursor, increased the amount of TSH released by TRH. Superfusion with TXB2 or imadazole, an inhibitor of TX synthetase, did not change TSH secretion. PGs A2, B2, D2, F1 alpha, F2 alpha, and endoperoxide analogs U-44069 and U-46619 had no effect on hormone release. PGE1 and E2 both increased TRH-stimulated TSH, but neither compound affected basal output; PGI2 was found to stimulate TSH release. Somatostatin inhibited TRH-induced TSH, but failed to block the effects of the PGs. These studies demonstrate that PGs, but no TXs, play a role in TSH secretion. PGE1 and PGE2 appear to modulate TRH responsiveness, while PGI2 directly stimulates hormone output.

Animals↗
PubMed1981

Factors modulating the secretion of thyrotropin and other hormones of the thyroid axis.

The first portion of this paper is devoted to an overview of the normal function of the hypothalamo-pituitary-thyroid axis. This section emphasizes areas of current research interest and it identifies several sites and mechanisms that are potentially important interfaces with toxins or toxic mechanisms. We then describe an in vitro technique for the continuous superfusion of enzymatically dispersed pituitary cells; this approach is particularly valuable in studying the dynamics of the TSH responses to the factors known (or suspected) to regulate TSH secretion in vivo. Using this technique, we have found that 10(-5)M prostaglandin (PG)I2 stimulates TSH secretion without altering the response to TRH (10(-8)M), and that this stimulation is not due to its rapid conversion to 6-keto PGF1 alpha. In contrast PGs of the E series (PGE1 and PGE2, 10(-5)M) increase responsiveness to TRH but have no effect alone. We found no effects of any of the other prostanoids tested (PGs A2, B2, F1 alpha, F2 alpha, thromboxanes A2 and B2, and the endoperoxide analog, U-44069. Somatostain (10(-9)M inhibits TRH-induced TSH secretion, but does not alter the responsiveness to PGI2. These findings suggest that somatostatin blocks TSH secretion at a point that is functionally prior to the involvement of the PGs, and perhaps does so by blocking synthesis or limiting availability of selected PGs.

Animals↗
PubMed1981

Pharmacological studies of the involvement of hypothalamic prostaglandins in the regulation of thyrotropin secretion.

A case is made for the involvement of pituitary prostaglandins (PGs) in the regulation of thyrotropin (TSH) secretion by citing recent evidence that TSH release in vivo and in vitro is enhanced by treatment with exogenous PGs and is inhibited by drugs (e.g., indomethacin) that block PG synthesis. Pharmacological studies were then performed to test the hypothesis that hypothalamic PGs also affect TSH secretion indirectly via the appropriate hypothalamic hormones that regulate pituitary secretion. The inhibition of thyroidectomy-induced TSH secretion was used as an endpoint in choosing the best of several drugs purported to inhibit PG synthesis. The established effectiveness of indomethacin and aspirin were used for reference in testing the following drugs: naproxen, mefenamic acid, tranylcypromine, and phenelzine. Only naproxen was found to be effective, but since it was no more potent than indomethacin, the latter drug was used for subsequent work. Indomethacin was stereotaxically implanted into several hypothalamic regions known to regulate TSH secretion, and sequential plasma samples were analyzed for TSH by radioimmunoassay. Bilateral implants of indomethacin in the anterior hypothalamic area increased TSH secretion throughout the 72 hr period of study. Sham inplants at this site and indomethacin implants in other nearby sites were ineffective. These findings suggest that endogenous PGs play an inhibitory role in the hypothalamic regulation of pituitary secretion.

Animals↗
PubMed1978

Inhibition of corticotropin secretion by hypothalamic administration of indomethacin.

The importance of endogenous prostaglandins (PGs) in regulating CRF release was investigated by administering the PG synthesis inhibitor, indomethacin (Ind), in specific hypothalamic regions to adult female rats. Solid Ind pellets placed in the anterior hypothalamic area (AHA) significantly reduced the elevated levels of plasma corticosterone normally observed after the surgical stress of the stereotaxic procedure. Similar pellets placed in the hypothalamic median eminence region (ME) completely blocked the normal compensatory hypertrophy observed 48 h after unilateral adrenalectomy. Plasma corticosterone secretion in response to hemorrhage (1% b.w.) or laparotomy with intestinal manipulation (LAP) in dexamethasone pretreated rats was reduced by Ind pellets, or Ind in phosphate buffer (BUF), respectively, implanted 2 h prior to the stress. These data suggest that the PGs may be important in mediating CRF release in response to a variety of stimuli.

Adrenal Cortex↗
PubMed1977

Stimulation of ACTH secretion by indomethacin and reversal by exogenous prostaglandins.

The prostaglandin (PG) synthesis inhibitor, indomethacin, has been found to enhance adrenocorticotropin (ACTH) secretion upon injection directly into the anterior pituitary at a dose that is ineffective intravenously. Such stimulation was observed in combination with, and in the absence of, stimulation by a corticotropin-releasing factor (CRF) preparation. It was reversed to varying degrees by replacing certain PGs exogenously. It suggested that endogenous PGs in the anterior pituitary participate in the modulation of the sensitivity of this gland to the hypothalamic neurohormone, CRF.

Adrenocorticotropic Hormone↗
PubMed1977

In vivo inhibition of thyroid secretion by indomethacin.

Indomethacin (Ind) was administered to adult female rats to reduce endogenous prostaglandin (PG) synthesis in order to investigate the role of PGs in thyroid hormone secretin. This treatment markedly reduced thyroidal PGF levels (667.7 vs. 1822.1 pg/my, P less than .001). Although the plasma TSH concentrations were normal in the Ind-treated group (41.14 vs. 40.01 mug/100 ml), dramatic decreases were observed in plasma T3 (24.5 ca. 6.7 nf/100 ml, P less than .001) and T4 (5.6 vs. 0.7 mug/100 ml, P less than .001) levels...

Animals↗
PubMed1976

Hypothalamic and pituitary effects of prostaglandins on ACTH secretion.

Various prostaglandins (PGs) were tested for their effects on ACTH secretion upon injection into the anterior pituitary, basomedial hypothalamus, basolateral hypothalamus, or a tail vein in anesthetized female rats. In some experiments, the PGs were injected in combination with a CRF preparation. The greatest effect seen was the stimulation of ACTH (and presumably CRF) secretion exerted at the basomedial hypothalamus. At the anterior pituitary, the PGs alone were without effect, but they did decrease the magnitude of the response to subsequent CRF.

Adrenocorticotropic Hormone↗