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Biomedical subjects

R M MacLeod

Publications and source records attributed to R M MacLeod.

At least 145 records · Page 8Linked to original sources
PubMed1978

The biphasic regulation of prolactin secretion by dopamine agonist-antagonists.

The in vitro secretion of PRL by the pituitary gland is inhibited by low concentrations of dopamine. Dopamine receptor-blocking agents, haloperidol and pimozide, in concentrations between 10-100 nM, neutralize virtually completely the dopamine-mediated inhibition of PRL secretion. At these concentrations, the dopamine antagonists alone are without effect on PRL secretion. Higher concentrations of these agents, however, have a powerful action to inhibit PRL secretion. Perphenazine was without direct effect on the in vitro secretion of PRL. These observations may be of general importance to the study of dopamine action in other organ systems.

Animals↗
PubMed1978

Uncharged nuclear receptors for estrogen in breast cancers.

This study was undertaken to define the incidence and concentration of uncharged nuclear estrogen receptors (RN) in human breast cancer. The concentrations of RN and cytoplasmic uncharged receptor were determined on sucrose gradients following a 4-hr incubation at 4 degrees with 1.6 nM 17 beta-[3H]estradiol in 139 tumor specimens from 137 patients. RN was extracted from washed nuclear pellets in buffer containing 0.4 M KCl. The receptor molecule extracted had a high affinity for 17 beta-[3H]estradiol (Kd = 0.9 to 7.6 nM) and was specific for estrogen. The possibility of artifact due cytoplasmic contamination of the nuclear fraction or high-ionic-strength-induced exchange of charged nuclear receptors was rendered unlikely by validation experiments performed with pooled tumor tissue. Significant amounts of cytoplasmic uncharged receptor (greater than 7 fmol/mg protein) were found in 63.3% of the tumors. Similar significant amounts of RN were found in 29.5% of the tumors. Significant amounts of RN in the presence of undetectable cytoplasmic uncharged receptor were found in 2.9% of the tumors. The percentage of tumors that contain significant amounts of RN is approximately the same percentage of estrogen receptor-positive tumors that do not respond to ablative therapy.

Adult↗
PubMed1977

Prolactin in human and rat serum and cerebrospinal fluid.

Rats treated with haloperidol or bearing subcutaneous implants of prolactin-secreting tumors had elevated CSF prolactin levels compared to those observed in control rats. These levels were commensurate with the increased serum level of prolactin, although there appeared to be an upper limit to the CSF prolactin concentration. Patients with prolactin-secreting pituitary adenomas had elevated CSF hormone levels as compared to patients with non-endocrine neurologic disease. This obtained, regardless of whether the tumor was intra- or extrasellar in its growth. The implications for the route of entry of prolactin into CSF under both normal and abnormal conditions, and the potential role for CSF prolactin as part of a feedback regulatory system on pituitary prolactin release are discussed.

Adenoma↗
PubMed1977

Mechanism of increased prolactin secretion by sulpiride.

The effect of sulpiride, a neuroleptic agent, on the secretion of prolactin by the anterior pituitary gland of the rat was studied. A significant increase in serum prolactin was observed after subcutaneous administration of the drug. Although sulpiride (0-10 micronmol/1 or 0-14 mmol/1) had no effect on the secretion of newly synthesized or radioimmunoassayable prolactin in vitro, the drug significantly overcame the inhibitory action that dopamine (0-50 micronmol/1) exerted on prolactin secretion. Rats implanted with a prolactin-secreting pituitary tumour MtTW15 showed an inhibition of prolactin biosynthesis and release. Injection of these rats with sulpiride restored prolactin biosynthesis and release of the hormone toward normal levels. These results demonstrate that sulpiride has a direct effect on the pituitary antagonizing the inhibitory effects exerted by dopaminergic mechanisms, although the drug itself does not stimulate the secretion of prolactin in vitro. Sulpiride may have a direct action on the pituitary lactotrophs in vivo, but effects at higher centres have not been excluded.

Animals↗
PubMed1976

Control of prolactin secretion by the hypothalamic catecholamines.

The neuroendocrine control of prolactin secretion is very complex. Even though the hypothalamus exerts a profound inhibitory influence upon the secretion of this hormone, the mechanism(s) involved is poorly understood. The cerebrospinal fluid seems to be becoming increasingly important as regards neuroendocrine regulatory mechanisms involving prolactin. Pharmacological agents such as apomorphine and many of the ergot alkaloids are very effective inhibitors of the secretion of prolactin. Still other pharmacological agents such as DMPEA, alpha-methyldopa, reserpine, and certain of the phenothiazines are very effective in causing a stimulation of prolactin secretion.

Animals↗
PubMed1975

Evidence of existence of two isozymes of carbonic anhydrase in the anterior pituitary gland of female rats.

Two molecular forms of carbonic anhydrase were identified in the rat anterior pituitary gland. Electrophoretic and immunological studies disclosed that the low activity carbonic anhydrase (type B) was associated with the particulate fraction of the pituitary gland and the high activity carbonic anhydrase (type C) was localized in the soluble fraction. The 800 times g pellet contained 50% of the total activity of a pituitary homogenate prepared in 0.25 M sucrose, while the 105,000 times g supernatant accounted for an additional 30% of the total. The particulate enzyme was rendered soluble by treatment with Trition X-100. The activity of pituitary gland carbonic anhydrase was about 6 times greater in preparations from female rats as compared with males. The activity of carbonic anhydrase in the particulate fraction decreased, and the activity in the soluble fraction increased without a change in total activity following incubation in vitro of pituitary glands. The intracellular adjustment in enzyme activity was accompanied by the secretion of prolactin into the incubation medium by the pituitary gland. The secretion of prolactin and the solubilization of the particulate carbonic anhydrase was inhibited when the pituitary gland was incubated in the presence of 10-5 M dopamine.

Animals↗
PubMed1975

Thyrotropin-releasing hormone blockade of the ergocryptine and apomorphine inhibition of prolactin release in vitro.

The interaction of thyrotropin-releasing hormone (TRH) and ergocryptine or apomorphine in affecting prolactin secretion was examined. Ergocryptine and apomorphine inhibited the release of 3H-prolactin labeled in an in vitro incubation of the rat anterior pituitary and led to a retention within the gland of 3H-prolactin. TRH (1.4 X 10(-8) M) partially blocked the inhibitory effect of 4 x 10(10) M ergocryptine on 3H-prolactin release and totally blocked the effect on radioimmunoassayable prolactin release. TRH also completely blocked the inhibitory effects of 5 x 10(-8) M apomorphine on both 3H-prolactin and radioimmunoassayable prolactin release. Since TRH can also completely block the inhibitory effects of dopamine upon prolactin secretion, these results are consistent with apomorphine and ergocryptine stimulating "dopaminergic" sites and also further support the role of TRH as a prolactin-releasing factor.

Animals↗
PubMed1975

Comparison of two isozymes of carbonic anhydrase in the rat anterior pituitary gland and pituitary tumors.

Two isozymes of carbonic anhydrase (EC 4.2.1.1.) were compared in the anterior pituitary gland of non-tumor-bearing rats and in the hormone-secreting pituitary tumors. In contrast to the pituitary gland, which contained 60 to 70% of the total carbonic anhydrase in the particulate subcellular fraction, three hormone-secreting pituitary tumors were devoid of the particulate (Triton X-100-solubilized)enzyme activity. Another pituitary tumor, 7315a, contained particulate carbonic anhydrase, but the activity was only 45% of the activity of normal pituitary gland. During the development of the rat brain, the particulate (Triton X-100-solubilized) carbonic anhydrase activity was undetectable in prepartions up to 21 days of age (body weight, 47 g). After that age, the carbonic anhydrase activity in the particulate fraction increased rapidly and reached the adult level at 37 days (body weight, 120 g), while the activity in the soluble fraction increased gradually after birth and then reached a plateau at 30 days (body weight, 81 g). These data show that the isozyme pattern of carbonic anhydrase in pituitary tumor tissue resembles the pattern in fetal cells more than the pattern in adult tissue.

Animals↗