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Biomedical subjects

M A Greer

Publications and source records attributed to M A Greer.

At least 73 records · Page 4Linked to original sources
PubMed1987

Repetitive or continuous thyrotropin (TSH)-releasing hormone administration induces a biphasic rise in plasma TSH in euthyroid but not in hypothyroid rats.

In euthyroid rats, repetitive bolus injections of 0.1, 1, or 5 micrograms/100 g BW TRH every 15 min for 2 h produced a biphasic rise in the plasma TSH concentration. After an initial peak at 15 min, plasma TSH fell at 60 min to a nadir 50-80% of the 15-min peak, then rose again by 90 min to a plateau with approximately the same amplitude as the initial peak. Plasma TSH remained at this level until TRH injections were stopped at 2 h, then fell to the pre-TRH baseline by 3 h. A similar biphasic rise in plasma TSH was produced by constant infusion of 0.01, 0.1, or 1 microgram/min TRH for 3 h. If the dose of bolus TRH injected was increased at 45 min, the dip in plasma TSH at 60 min was significantly decreased. A single iv injection of 1 microgram/100 g BW T4 immediately or 4 h before the bolus TRH injections did not abolish the biphasic TSH response. However, the T4 injection 4 h before TRH significantly attenuated the amplitude of the TSH response. In hypothyroid rats, either repetitive bolus injections or constant infusion of TRH induced only a single peak of plasma TSH at 15-30 min, after which plasma TSH fell to and remained at the pre-TRH baseline. If the hypothyroid rats were injected with 2 micrograms/100 g BW T4 for 4 days before TRH bolus injections, a biphasic TSH response to continual TRH, identical to that in euthyroid rats, was produced. The pituitary TSH content of the hypothyroid rats was significantly subnormal. T4 treatment for 4 days restored both plasma and pituitary TSH levels to the euthyroid range. Our data indicate that 1) constant or repetitive exposure to TRH induces a biphasic rise in plasma TSH in euthyroid, but not in hypothyroid, rats; 2) this biphasic phenomenon is not produced by negative feedback of T4 on the thyrotroph; and 3) the rapid development of refractoriness to TRH in hypothyroid rats is not dependent on continuous exposure to a constant concentration of TRH, but may be related to the reduced TSH content of the hypothyroid thyrotroph.

Animals↗
PubMed1987

Diagnostic value of thyrotropin-releasing-hormone stimulation in patients with pituitary tumor.

Plasma prolactin response to thyrotropin-releasing-hormone (TRH) stimulation was diminished in 30 patients with prolactinomas and 9 patients with acromegaly who had normal serum prolactin levels. There was no overlap of prolactin responses when compared with 32 control patients. Responses of ten patients with adrenocorticotropin (ACTH)-secreting pituitary tumors were similar to those of controls. Plasma growth hormone concentrations after TRH stimulation changed significantly in 28% of normal control and 20%, 25% and 50% of patients with prolactin-, growth hormone- and ACTH-secreting pituitary tumors, respectively. Our data suggest that the blunted TRH-induced rise in plasma prolactin levels in patients with prolactinomas and those with acromegaly may be related to humoral factor(s) affecting TRH receptor or postreceptor function. Growth hormone responses to TRH are nonspecific and should not be considered a marker for active acromegaly.

Female↗
PubMed1986

Type-II thyroxine 5'-deiodinase is present in the rat pineal gland.

Thyroxine-5'-deiodinase has been identified in the rat pineal gland. The characteristics of the enzyme are compatible with a Type-II deiodinase which is tissue-specific and presumably related to generating a local action of thyroid hormone. Our data suggest there may be a previously unrecognized role of thyroid hormone in the regulation of pineal activity.

Animals↗
PubMed1986

Stimulation of corticosterone secretion in vitro by brief ACTH exposure.

We examined the relationship between ACTH concentration and exposure duration on stimulation of corticosterone (B) secretion in vitro using perifused enzymatically dispersed rat adrenocortical cells. A modular perifusion apparatus was used that permitted evaluation of 20-24 cell chambers per experimental session. In expt 1, 20-1000 pg/ml concentrations of synthetic ACTH-(1-24) were presented to cells for 1 min. In expt 2, 100 pg ACTH-(1-24) was presented to adrenal cells in five dose-duration regimens ranging from 5 pg/min for 20 min to 100 pg/min for 1 min. Perifusal rate was 1 ml/min in all sessions. B was determined by radioimmunoassay. In expt 1 (constant-duration paradigm), 1-min presentation of ACTH-(1-24) produced log-linear dose-response effects across these concentrations (r = 0.926, P less than 0.01). In expt 2 (constant-mass paradigm), identical masses administered in different dose-duration regimens had different steroidogenic efficacies (P less than 0.02): low-dose long-duration regimens provoked greater total release than high-dose short-duration regimens. Overall, every dose-duration regimen was associated with stimulation of B secretion. These results indicate that very brief exposure to physiological concentrations of ACTH-(1-24) is a significant stimulus for corticosteroid secretion; variations in the dose-duration regimen over the physiological range modifies both the maximum rate of secretion and the duration of secretion, but not the response latency; and ACTH-(1-24) presentation mass is not the sole determinant of B secretion.

Adrenal Cortex↗
PubMed1986

Dynamics of thyrotropin-releasing hormone-induced thyrotropin and prolactin secretion by acutely dispersed rat adenohypophyseal cells. Evidence for 'all-or-none' secretion by heterogeneous secretory units, each with a specific response threshold.

We have examined the dynamics of thyrotropin-releasing hormone (TRH)-stimulated secretion of prolactin (PRL) and thyrotropin-stimulating hormone (TSH) using enzymatically dispersed rat adenohypophyseal cells suspended in a perfusion chamber with a volume of 0.2 ml to minimize mixing and dilution. One-min exposure to 3-300 nM TRH, the effective dose range, elicited immediate pulses of PRL and TSH secretion with dose-dependent amplitudes. At all TRH concentrations, following a brief burst of secretion lasting less than 1 min, release of both hormones declined precipitously. Increasing the duration of stimulation up to 30 min with half-maximal TRH concentrations did not alter the dynamics of the initial response and was ineffective in maintaining the initial amplitude of secretion. This phenomenon could not be attributed to exhaustion of readily releasable intracellular PRL and TSH, since an increment in TRH concentration elicited a second pulse of hormone secretion with temporal response characteristics identical to the first. The amplitude of the second pulse was dependent on both the initial concentration of TRH and the magnitude of the increment in TRH concentration. With a stepwise increase in TRH concentration during continuous perfusion, the sum of PRL or TSH secreted from all bursts of secretory activity approximated that achieved with a single exposure to the highest concentration of TRH employed. The high-amplitude secretory response to a given concentration of TRH was restored after an 8-min perfusion with medium alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Comparison of the ability of thyroxine and triiodothyronine to suppress TRH-induced TSH secretion by perfused rat anterior pituitary fragments.

Adenohypophyseal fragments from 8 rats were perifused in small 0.2-ml chambers with medium alone or with medium containing 0.2 or 2 micrograms/dl T3 or 20 micrograms/dl T4. The TSH secretion in response to 1-min perifusion with 3 X 10(-8) M TRH was measured before and at 20- to 40-min intervals after beginning T4 or T3 perifusions. A similar temporal course of inhibition of TRH-induced TSH secretion was produced by both iodothyronines, suggesting but not proving that T4 may inhibit the TSH secretion by a direct effect not dependent on its prior intra- or extrapituitary conversion to T3.

Animals↗
PubMed1985

Comparison of hyposmolar and hyperosmolar effects on in vitro luteinizing hormone secretion by anterior pituitary cells.

It has previously been described that perifusion of acutely dispersed adenohypophyseal cells with hypotonic medium causes an immediate high-amplitude "on" burst of luteinizing hormone (LH) secretion. In the present report the converse study with hyperosmolar solutions has been made. Perifusion with hypertonic medium depressed LH secretion; return to isotonicity caused an immediate high-amplitude "off" burst of LH secretion closely resembling that induced by hypotonic perifusion. The data give further support to the theory that exocytotic secretion may involve expansion of the outer cell membrane, thus drawing secretory granules to the cell surface where their contents are extruded.

Animals↗
PubMed1984

In vivo and in vitro comparisons of biological activities of bovine, ovine and rat CRF (corticotrophin-releasing factor).

The biological activity of partially purified bovine hypothalamic CRF (corticotrophin- releasing factor) was compared to those of synthetic CRFs (ovine, rat) sauvagine and vasopressin in vivo and in vitro. ACTH-primed hypophysectomized rats with heterotopically transplanted pituitaries and medial basal hypothalamic ablation (H-T + MBHA ), and intact rats pre-treated with chlorpromazine, morphine and Nembutal (C-M-N) were used for in vivo CRF assays. Perifused rat adenohypophyseal fragments were employed for in vitro studies. CRF-A (void volume fractions, 'big' CRF) and CRF-B (Kav = 0.583) purified from bovine hypophyseal stalk, synthetic ovine and rat CRF, and sauvagine all induced significant stimulation of ACTH and/or corticosterone secretion in these systems. Synthetic ovine and rat CRF and sauvagine showed comparable CRF potency. The CRF dose-response slopes for bovine CRF were somewhat steeper than those for ovine CRF or sauvagine in the in vitro system. Vasopressin had the least steep dose-response slope. Intravenous bolus administration of ovine CRF caused a more prolonged (greater than 20 min) elevation of plasma ACTH compared to a relatively short duration after bovine CRF-A. These data suggest that bovine hypothalamus contains substance(s) which exhibits different CRF characteristics from those of ovine CRF.

Adrenocorticotropic Hormone↗
PubMed1983

Nycterohemeral difference in inhibition of stress-induced ACTH in adrenalectomized rats.

To determine the interactions among the determinants of ACTH secretion, we examined the influence of circadian rhythmicity on glucocorticoid suppression of ACTH. Adrenalectomized rats were injected with the same amount of corticosterone at 0900 and 1800 h, and plasma ACTH concentrations were determined under basal conditions and after a standard ether stress. At 0900 h, corticosterone suppressed both basal and stress-induced plasma ACTH concentrations. At 1800 h, the same treatment suppressed basal ACTH secretion but not the stress-induced rise. Although the same amount of corticosterone was injected at both times of day, the plasma corticosterone concentration 5 min after injection was higher at 1800 h than at 0900 h. This study indicates that there is a nycterohemeral difference in feedback suppression of stress-induced ACTH secretion by a given dose of corticosterone. The daily variation in feedback inhibition may be due to the additive effect of the evening surge stimulus and the stress stimulus that together override the feedback signal.

Adrenalectomy↗
PubMed1983

In vitro TSH and PRL secretion from eutopic and heterotopic rat pituitaries: effects of hypothyroidism.

Five adenohypophyses from donors of the same strain, age, and sex were transplanted under the renal capsule of young adult female rats. At least 3 wk later, enzymatically dispersed cells from eutopic or heterotopic adenohypophyses from the same rat were perifused in vitro in a small chamber. Thyrotropin (TSH) and prolactin (PRL) secretion per 10(6) cells were significantly less from heterotopic than from eutopic cells under all conditions. In cells from euthyroid animals, TRH induced TSH secretion only in the eutopic cells but induced PRL secretion in both eutopic and heterotopic cells. Hypothyroidism increased TRH-induced TSH secretion and content in the cell lysate in both eutopic and heterotopic cells but increased TRH-induced PRL secretion only in the eutopic cells. The increase in TSH secretion induced by hypothyroidism in the heterotopic cells was of borderline statistical significance. The inability of TRH to induce TSH secretion in heterotopic pituitary cells from euthyroid rats may be due to a lower set point for thyroid hormone inhibition of TSH secretion in the heterotopic thyrotrophs. Heterotopic pituitary TSH secretion is probably suppressed by the normal plasma thyroid hormone concentration maintained by the eutopic pituitary and may be stimulated by TRH only in the presence of a subnormal plasma thyroid hormone concentration.

Animals↗
PubMed1983

Hyposmolar stimulation of in vitro pituitary secretion of luteinizing hormone: a potential clue to the secretory process.

Diluting the perifusion medium with water caused a striking prompt increase in LH secretion from perifused, acutely dispersed adenohypophseal cells. The minimum effective proportion of water was 4%; the quantity of hormone secreted was proportional to the dilution of the medium up to greater than 50% water. Secretion was not induced if the dilution was made with 5% aqueous mannitol to maintain isotonicity. The LH secretory responses to hyposmolarity or to LHRH were qualitatively indistinguishable. We suggest that expansion of the outer cell membrane may be an important initial component of the mechanism of secretion from adenohypophyseal cells.

Animals↗
PubMed1982

In vivo adrenocorticotropin-releasing activity of neurohypophyseal hormones and their analogs.

The ability of 21 neurohypophyseal hormones and related synthetic peptides to raise plasma ACTH or corticosterone concentrations was studied in female rats anesthetized with chlorpromazine, morphine, and pentobarbital. Corticotropin-releasing factor (CRF) activity was significantly correlated with pressor but not with antidiuretic or oxytocic activity. However, peptides with little or no pressor but very potent antidiuretic activity had weak CRF activity if given in a dose greater than 4 antidiuretic units/100 g BW; the dose-response slopes of these analogs were significantly flatter than that of arginine vasopressin. Pretreatment with antagonists with antipressor but not antiantidiuretic activity consistently reduced the CRF activity of the analogs with potent pressor activity. We conclude that the CRF activity of the neurohypophyseal hormones is primarily related to pressor activity.

Adrenocorticotropic Hormone↗
PubMed1982

The importance of the hypothalamic lateral retrochiasmatic area in the control of adrenocorticotropin and thyrotropin secretion.

Anterolateral hypothalamic deafferentiation was made in rats to explore the importance of the neural pathways through the lateral retrochiasmatic area (RCAL) in the regulation of ACTH and TSH secretion. In rats with complete bilateral RCAL transection, pituitary-adrenal function was altered in the following respects compared to sham-operated controls. 1) Basal plasma ACTH, corticosterone (B), and adrenal weight were depressed. 2) Plasma ACTH and B elevation in response to 3-min ether inhalation were markedly decreased or abolished. 3) Insulin-induced hypoglycemia produced no or little plasma B elevation. 4) Lysine-vasopressin was significantly less effective in inducing pituitary-adrenal activation. Reductions in plasma ACTH and B concentrations and adrenal weight were correlated with the completeness of the RCAL transection. The plasma TSH concentration was lower in the deafferented rats than in the controls regardless of the completeness of the cut at the RCAL, indicating that the neural pathways traversing this area do not possess a critical importance for the regulation of TSH if the rest of the hypothalamus is deafferented anterolaterally. We conclude that intact neural connections between the medial basal hypothalamus and the central nervous system at the RCAL are essential for the maintenance of normal hypothalamic-pituitary-adrenal function.

Adrenal Glands↗
PubMed1982

Differential effects of dithiothreitol and iodoacetamide on corticotropin-releasing factor (CRF) activity of bovine hypothalamic CRFs and vasopressin.

Various fractions were tested in vivo for corticotropin-releasing factor (CRF) activity after Sephadex G-100 fractionation of 0.1-N HCl extracts of bovine hypophyseal stalk or cerebral cortex. Female rats pretreated with chlorpromazine, morphine, and Nembutal were used for CRF assay. CRF-A (void volume fractions; big CRF), CRF-B (Kav = 0.583), and CRF-C (salt volume fractions) of bovine hypophyseal stalk and lysine or arginine vasopressin all induced clear-cut stimulation of ACTH and corticosterone in the assay rat, whereas they were ineffective in acutely hypophysectomized rats. Control fractions purified from bovine cerebral cortex had no CRF activity. Treatment of arginine and lysine vasopressin and CRF-C with dithiothreitol and iodoacetamide completely abolished their CRF activity, whereas the CRF activities of CRF-A and CRF-B were unaltered by these treatments. Treatment with iodoacetamide alone had no effect on the CRF activity of any of these substances. Fractionation of either CRF-C or arginine vasopressin on Sephadex G-15 yielded a CRF-active peak at a Kav of 0.35. We conclude that 1) three different forms of CRF exist in bovine hypophyseal stalk; 2) CRF-A and CRF-B are unrelated to vasopressin and require neither a disulfide bond(s) nor a sulfhydryl group(s) for their CRF activity; 3) reduction of the disulfide bond of vasopressin destroys both CRF and antidiuretic activities; 4) CRF-C requires an intact disulfide bond(s) for its CRF activity and is likely to be either vasopressin itself or a substance closely related to vasopressin; and 5) CRF-B is likely to be the physiologically important form of bovine CRF.

Adrenocorticotropic Hormone↗
PubMed1982

Follow-up comparison of short-term versus 1-year antithyroid drug therapy for the thyrotoxicosis of Graves' disease.

We have treated 68 thyrotoxic patients with Graves' disease with a single daily dose of 30 mg methimazole until they were clinically euthyroid and their plasma thyroid hormone concentrations were within normal limits. Sixteen of 56 patients (29%) treated 4.8 +/- 0.2 months (mean +/- SEM; range, 1.5-8.5 for their initial attack of thyrotoxicosis have remained in remission for 54.4 +/- 7.7 months (range, 12-105). Twenty-seven of the patients who relapsed were treated with a subsequent 1-yr course of methimazole. Five of these patients (19%) have maintained a remission for 29.6 +/- 10.8 months (range, 3-66); the remainder relapsed after 7.1 +/- 2.3 months (range, 1-50). If the patients lost to follow-up while known to still be in remission are excluded, the sustained remission rate is 12 of 52 (23%) for initial short term therapy and 3 of 25 (12%) for the subsequent 1-yr of antithyroid treatment. The results of short term antithyroid drug treatment in 12 patients previously treated with long term antithyroid drugs or thyroidectomy were similar, but the follow-up period was not as long. Short term antithyroid drug therapy is a potentially long lasting, innocuous, and relatively inexpensive program for the treatment of Graves' disease, especially for patients with small goiters.

Antithyroid Agents↗