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Biomedical subjects

R M MacLeod

Publications and source records attributed to R M MacLeod.

At least 127 records · Page 7Linked to original sources
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

Effect of antiestrogens on pituitary prolactin production in normal and pituitary tumor-bearing rats.

Administration of the antiestrogen tamoxifen to normal Buffalo female rats caused a 45% reduction (p less than 0.01) in 3H-prolactin synthesis and release in vitro. Radioimmunoassayable prolactin in incubated glands and medium also decreased significantly. Similar results were observed in Wistar-Furth animals except for in vitro radioimmunoassayable prolactin, which decreased less markedly (by 33%, p less than 0.01). Serum prolactin concentration in treated rats was unchanged. Tamoxifen did not affect the extremely high serum prolactin concentration in rats bearing mammotropic tumors. It further reduced in vitro synthesis of radioactive prolactin but not of the radioimmunoassayable hormone. No interaction between antiestrogens and the dopamine agonist bromocriptine was observed. These observations suggest that the nonsteroidal antiestrogens decrease the synthesis of prolactin but have little effect on release of the hormone. Tamoxifen inhibits growth of transplantable mammotropic tumors MtTW15 and 7315a potently without altering tumor prolactin production. In vivo treatment of adult female rats with tamoxifen did not affect in vitro synthesis and release of radioactive growth hormone, but reversed the elevated growth hormone production of rats bearing 7315a tumors.

Animals↗
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↗
PubMed1980

Estrogen receptors in nasopharyngeal angiofibromas.

Nasopharyngeal angiofibromas, which occur exclusively in pubescent males, are frequently treated with estrogens in an effort to decrease their size and vascularity. It has been presumed by some that estrogen has a direct effect on the tumor itself. Others have felt that hormone acts by affecting the pituitary-gonadal axis. In this study, six male patients with nasopharyngeal angiofibromas had their tumors analyzed for estrogen receptors and none were found. Despite this fact, two of these patients treated with estrogens showed clinical evidence of a decrease in tumor size and vascularity. This response occurring in the absence of estrogen receptors suggests that the action of estrogen on nasopharyngeal angiofibromas is indirect. Alternatively these tumors may be testosterone dependent and the administration of estrogen suppresses the normal male testosterone levels, with a resultant reduction in tumor size and vascularity. Twenty-four patients with nasopharyngeal angiofibroma have been treated at the University of Virginia in the past 22 years. The average blood loss at operation was 1900 cc. When estrogens were administered preoperatively in 3 patients, the average blood loss was 1135 cc. Those patients who received no estrogens averaged 2000 cc blood loss. These figures do not reflect the size or extent of the disease, both of which greatly influence blood loss.

Adolescent↗
PubMed1979

Effects of iodine deficiency and high-fat diet on N-nitrosomethylurea-induced mammary cancers in rats.

The effects of an altered content of dietary iodine and fat on the development of N-nitrosomethylurea-induced mammary tumors in rats were studied and correlated with thyroid and pituitary function studies. In three separate experiments, animals fed a semisynthetic diet containing 11.8% fat had an earlier time of tumor appearance and greater tumor burden than did controls maintained on a diet containing 4.6% fat. These diet-associated changes were markedly inhibited by ovariectomy, indicating that the tumor growth was hormone responsive. We examined the possibility that the diet with increased fat content enhanced tumor growth through alterations in prolactin metabolism but could find no consistent elevation in serum prolactin and no increase in pituitary prolactin synthesis in vitro. Our data further showed that rats on an iodine-deficient form of the high-fat diet had no greater tumor growth than did animals receiving an iodine-supplemented form of the same diet. We conclude from these results that iodine deficiency does not promote mammary tumorigenesis. An incidental finding of great interest was that ovariectomy led to a highly significant depression of thyroid-stimulating hormone production in vitro. This suggests that estrogens may directly influence thyroid-stimulating hormone synthesis in vivo and thus contribute to the sex-related differences in thyroid physiology.

Animals↗
PubMed1978

Binding of dopamine to bovine anterior pituitary gland membranes.

[3H]-dopamine (DA) binding to bovine anterior pituitary membranes were measured using sensitive in vitro ultrafiltration and centrifugation techniques. The specific interaction of [3H]-DA with the membrane fraction reached a steady-state level within 15 min at 30 degrees C and was reversible by incubating with excess nonradioactive DA. Scatchard analysis suggests the presence of 2 sites for DA specific binding having Kd values of 4.4 x 10-10 M and 4.7 x 10-8 M, respecively. Correspondingly, the total receptor concentrations were calculated to be 336 and 2,340 pmoles/g protein. Blockade of [3H]-DA binding was produced most effectively by ergocryptine and apomorphine. Perphenazine and haloperidol were considerably less active and primozide did not compete. The importance of DA in the regulation of prolactin (Prl) secretion and the characterization of pituitary DA receptor sites are discussed.

Animals↗