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Biomedical subjects

M O Thorner

Publications and source records attributed to M O Thorner.

At least 235 records · Page 13Linked to original sources
PubMed1981

Dopaminergic mechanisms and luteinizing hormone (LH) secretion. II. Differential effects of dopamine and bromocriptine on LH release in normal women.

After our observation of the failure of bromocriptine to inhibit LH secretion in hyperprolactinemic women, we have investigated the effects of bromocriptine and dopamine (DA) on LH secretion in normal ovulatory women within 5 days of the midcycle LH peak. Both bromocriptine (2.5 mg, orally) and DA (4 micrograms/kg . min, iv) for 4 h lowered serum PRL levels by more than 80%. Bromocriptine was ineffective in suppressing LH secretion and, in fact, resulted in a slight but significant stimulation, while, in contrast, DA was effective in lowering circulating LH levels by approximately 30% and reducing spontaneous LH fluctuations. The dissociation of the effects of these two dopaminergic agents on LH secretion may be explained by the existence of multiple DA receptors. The slight stimulatory effect of bromocriptine might be due to a preferential presynaptic action of bromocriptine inhibiting endogenous DA secretion in the hypothalamus and thus reducing this catecholamine's tonic inhibitory influence on LH secretion.

Adult↗
PubMed1981

Pergolide mesylate: its effects on circulating anterior pituitary hormones in man.

Pergolide mesylate is a synthetic ergoline with dopamine agonist properties. The endocrine profile was studied in a double blind crossover design in six normal males. Circulating PRL, TSH, GH, LH, FSH, and cortisol were measured in the basal state and after TRH (500 micrograms iv) administration at 4.5, 11.5, and 23.5 h after placebo or pergolide (100 micrograms orally). Pergolide caused suppression of basal PRL from 2-8 ng/ml to less than 2 ng/ml commencing 60 min after administration and persisting throughout the 23.5-h study period. For the three TRH tests, a suppression of peak PRL (mean +/- SEM) response to TRH of 54.6 +/- 5.1 vs. 1.9 +/- 0.5, 45.2 +/- 4.1 vs. 4.5 +2- 0.6, and 34.4 +/- 2.9 vs. 6.9 +/- 1.4 ng/ml, respectively, for placebo and pergolide was noted. Basal TSH levels were unaffected by pergolide, but after pergolide the peak TSH response to the first two TRH challenges was blunted (placebo vs. pergolide: 12.3 +/- 1.2 vs. 6.8 +/- 1.0 and 14.8 +/- 2.0 vs. 9.6 +/- 1.0, respectively); however, the third TSH response (9.8 +/- 1.1 vs. 9.3 +/- 1.2) was not blunted after pergolide. GH secretion was stimulated by pergolide with a consistent pulse observed within 60 min of pergolide administration and an enhancement in the number and amplitude of subsequent GH pulses throughout the 24-h period. Cortisol levels rose after pergolide and returned to levels seen on the control day at 16.5 h. FSH levels were unaffected but LH levels were lowered pergolide. Side effects including nausea, vomiting, and hypotension were observed in all subjects. Pergolide is a potent dopamine agonist with the anticipated endocrine profile and clinical effects; its long duration of actions offers promise of single daily dose therapy for hyperprolactinemia.

Adult↗
PubMed1981

Prolactin secretion in Parkinson disease.

We studied the dopaminergic control of lactotroph cells in the anterior pituitary of parkinsonian patients and age-matched normal subjects. The resting levels of prolactin and the TRH-induced rise in prolactin were normal in Parkinson disease. Levodopa elicited a normal suppression of prolactin concentrations in parkinsonian subjects; the major abnormality to emerge was attenuation of the response to thyrotropin-releasing hormone (TRH) in the parkinsonian patients following administration of Sinemet (levodopa plus carbidopa) or bromocriptine. These findings imply pathology of extrastriatal dopamine systems in Parkinson disease. Since the addition of carbidopa enhanced the suppression of prolactin induced by levodopa, exogenous levodopa probably acts predominantly through the formation of dopamine in the hypothalamus, but inside the blood-brain barrier, rather than as a direct effect of circulating dopamine on the anterior pituitary or areas of the hypothalamus outside the blood-brain barrier.

Adult↗
PubMed1980

Dopaminergic inhibition of metoclopramide-induced aldosterone secretion in man. Dissociation of responses to dopamine and bromocriptine.

This study was designed to investigate the role of dopaminergic mechanisms in the control of aldosterone secretion in man. Five normal male subjects in metabolic balance at 150 meq sodium/d and 60 meq potassium/d constant intake received the specific dopamine antagonist, metoclopramide, 10 mg i.v. on 2 consecutive d. On the 1st d, the subjects received an infusion of 5% glucose solution (vehicle) from 60 min before to 60 min after metoclopramide administration; on the 2nd d, an infusion of dopamine 4 mug/kg per min was substituted for vehicle. Metoclopramide in the presence of vehicle increased plasma aldosterone concentrations from 2.4+/-1.1 to a maximum of 17.2+/-2.8 ng/100 ml (P < 0.01) and serum prolactin concentrations from 7.5+/-5.0 to a maximum of 82.2+/-8.7 ng/ml (P < 0.01). Dopamine 4 mug/kg per min did not alter basal plasma aldosterone concentrations, but blunted the aldosterone responses to metoclopramide significantly; in the presence of dopamine, plasma aldosterone concentrations increased from 3.1+/-0.5 to 6.2+/-1.4 ng/100 ml (P < 0.05) in response to metoclopramide. The incremental aldosterone responses to metoclopramide were significantly lower in the presence of dopamine than with vehicle. Dopamine 4 mug/kg per min suppressed basal prolactin to <3 ng/ml and inhibited the prolactin responses to metoclopramide; serum prolactin concentrations increased to a maximum of 8.5+/-2.3 ng/ml with metoclopramide in the presence of dopamine. The subjects were studied in the same manner except that dopamine 2 mug/kg per min was administered instead of the 4-mug/kg per min dose. Dopamine 2 mug/kg per min attenuated the aldosterone and prolactin responses to metoclopramide, but was less effective than the 4-mug/kg per min dose of dopamine. Metoclopramide 10 mg i.v. was administered to five additional subjects after pretreatment with the dopamine agonist, bromocriptine, 2.5 mg or placebo at 6 p.m., midnight, and 6 a.m. before study. Bromocriptine suppressed basal serum prolactin levels and completely inhibited the prolactin responses to metoclopramide. In contrast, bromocriptine did not alter basal plasma aldosterone concentrations or the aldosterone responses to metoclopramide. Plasma renin activity, plasma cortisol, and serum potassium concentrations were unchanged by metoclopramide, dopamine, or bromocriptine. The results of this study suggest that the aldosterone response to metoclopramide is mediated by metoclopramide's antagonist activity at the dopamine receptor level. The results further suggest dissociation of the responses to the dopamine agonists, dopamine and bromocriptine, and indicate that a new type of dopamine receptor may inhibit aldosterone secretion.

Adult↗
PubMed1980

Dopaminergic mechanisms and luteinizing hormone secretion. I. Acute administration of the dopamine agonist bromocriptine does not inhibit luteinizing hormone release in hyperprolactinemic women.

The concept that domapinergic mechanisms control LH secretion by modulation of gonadotropin-releasing hormone (GnRH) has been recently investigated in man. Since hyperprolactinemia is associated with increased hypothalamic dopamine turnover (which may reflect increased dopaminergic activity), inhibition of GnRH by dopamine in this situation would be maximal. Additional stimulation of dopamine receptors by a dopamine agonist would not be expected to result in further inhibition of LH release. Twelve hyperprolactinemic women were studied on 2 days during which measurements of serum PRL and LH were made over 11.5 h. Day 1 served as a control for day 2 when 2.5 mg of the dopamine agonist bromocriptine were administered orally at 0900 h. While serum PRL and LH levels on day 1 showed small fluctuations (+/- 10%), serum PRL on day 2 fell by 82%. Serum LH concentrations on day 2 remained unchanged. The demonstration or the efficacy of bromocriptine in lowering PRL levels documents the expected increase in dopaminergic tone; however, the lack of effect of bromocriptine in surpressing LH release suggests that either there is already maximal endogenous inhibition of GnRH in hyperprolactinemic women or, alternatively, that dopaminergic mechanisms are unimportant in the control of LH secretion.

Adult↗
PubMed1980

Rapid regression of pituitary prolactinomas during bromocriptine treatment.

Therapy for large prolactinomas remains controversial. Surgery is often unsuccessful in restoring endocrine function to normal. However, medical therapy with bromocriptine, a dopamine agonist, not only suppresses PRL levels, but may also lead to a reduction in tumor size. Previous reports have demonstrated radiographic evidence of tumor regression only after 3 or more months of bromocriptine therapy. We have now documented, for the first time, objective evidence of extremely rapid reduction in tumor size in two patients harboring large PRL-secreting pituitary tumors (mean pretreatment serum PRL levels, 2350 and 3900 ng/ml) who were prospectively treated with bromocriptine (7.5 mg/day) in preference to surgical intervention despite marked visual impairment in one of the patients. After 2 and 6 weeks of therapy, respectively, marked reduction in tumor size was demonstrated radiographically in both patients. Headache, visual acuity, and visual fields had improved after only 3 days. Although the mechanism of bromocriptine's antitumor activity is unclear, we believe that a large prospective trial to study the effects of bromocriptine therapy on the size of PRL-secreting macroadenomas is urgently needed to determine whether medical therapy should become the primary modality of treatment to reduce tumor size as well as restore endocrine function.

Adenoma↗
PubMed1979

Pregnancy in patients presenting with hyperprolactinaemia.

Ninety-two pregnancies occurred in 76 hyperprolactinaemic patients treated with bromocriptine. Half conceived within three months of attempted conception. There was no evidence of an increased rate of spontaneous abortion, fetal abnormality, or multiple pregnancy; the three twin pregnancies occurred in women who were additionally treated with clomiphene and human chorionic gonadotrophin. Thirty-one patients had radiological evidence of a pituitary tumour; 14 with major radiograph changes in the pituitary fossa or serum prolactin concentrations greater than 100 ng/ml received pituitary irradiation before conception. None of the latter showed evidence of enlargement of the tumour during pregnancy. In contrast two of the four patients with similar tumours but who were not irradiated developed visual field defects, one with gross destruction of the pituitary fossa. Prophylactic treatment to limit subsequent tumour expansion during pregnancy in patients with prolactinomas is indicated, and pituitary irradiation before conception appears to be a safe and effective method to achieve this goal.

Bromocriptine↗