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Biomedical subjects

M Ferin

Publications and source records attributed to M Ferin.

At least 91 records · Page 5Linked to original sources

Dopaminergic and serotonergic involvement in opiate-induced prolactin release in monkeys.

The present experiments were performed to determine the site of action (hypothalamic or hypophyseal) and the mechanism (dopaminergic or serotonergic) by which morphine increases PRL in monkeys (Macaca mulatta and Macaca nemestrina). To determine the site of action, 9 mg morphine were injected iv to four intact and four pituitary stalk-sectioned monkeys. PRL concentrations rose significantly (P less than 0.01) from less than 5 ng/ml to an average maximum value of 208 +/- 20 ng/ml at 15 min in intact animals, but remained unchanged in pituitary stalk-sectioned animals. There was a significant reduction (P less than 0.01) of this response in intact monkeys that received 5 mg L-dopa, iv, 5 min before the morphine stimulus. In these animals, PRL only rose to 100 +/- 46 ng/ml. In contrast, the PRL response in four monkeys pretreated with 5 or 20 mg methysergide, iv (a serotonin receptor blocker), 5 min before the opiate stimulus was not different from in controls. Likewise, the daily administration of 100 mg p-chlorophenylalanine, sc (a serotonin synthesis blocker), for 6 days failed to alter the PRL response to morphine. These data suggest that opiates increase PRL via a neural site of action and that the mechanism may involve dopaminergic but not serotonergic pathways.

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Endocrine function in the Klüver-Bucy syndrome: studies in adult female rhesus monkeys.

Although the behavioral abnormalities of the Klüver-Bucy syndrome are well known, an investigation of the endocrine parameters had not been undertaken previously. The authors report normal reproductive cyclicity (including preserved feedback mechanisms) and growth hormone and cortisol secretion patterns in female rhesus monkeys with the syndrome. It is concluded that the abnormal behavior seen in the Klüver-Bucy syndrome is not associated with abnormalities of the reproductive mechanisms.

Animals↗

Section of the pituitary stalk in the rhesus monkey: morphological and endocrine observations.

The effect of sectioning the pituitary stalk on the hypothalamic magnocellular system of the rhesus monkey was studied by specific immunocytochemical techniques. Regeneration of the proximal stump with reconstitution of a "new" neurohypophysis occurred as early as three weeks after operation, illustrating the remarkable regenerative ability of the system. The functional capacity of the newly formed neurovascular units was also tested, and the results indicate that they not only resume basal secretion of posterior pituitary hormones, but are also able to increase their output in response to a variety of challenges.

Animals↗

Section of the pituitary stalk in the rhesus monkey. I. Endocrine studies.

The effects of pituitary stalk section on anterior pituitary secretion were studied in 20 female rhesus monkeys. Vascular connections between the hypothalamus and the pituitary gland were permanently interrupted in all but 4 animals. Prolactin levels rose rapidly and remained significantly elevated in all effectively stalk-sectioned animals for as long as the observation period (up to 3 years). Only smaller and transient elevations of prolactin were seen in the animals in which revascularization of the anterior pituitary gland had occurred. Growth hormone and cortisol were significantly decreased after stalk section, and were not released by insulin. Radioimmunoassayable luteinizing hormone (LH) levels decreased following surgery and, by bioassay, LH became undetectable within 5 weeks after stalk section, indicating that gonadotropin-releasing hormone is essential for the viability of the gonadotrope. The results indicate that plasma prolactin concentrations can be used to monitor completeness of pituitary gland isolation from direct hypothalamic influence. Stalk-sectioned monkeys provide good models to study direct pituitary effects of various hormones or drugs.

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Section of the pituitary stalk in the rhesus monkey. II. Morphological studies.

The effects of pituitary stalk section on anterior pituitary morphology were studied in 18 female rhesus monkeys. 4 animals were studied within 1--14 days after the operation, while the others were examined later (average 17.2 months). In 3 monkeys there was no necrosis of the anterior lobe, whereas in the remaining animals, an area of infarction averaging 20% was found. Using immunocytochemical techniques, we found that corticotropes and somatotropes were still present following the procedure, and that the number of lactotropes increased markedly. In contrast, gonadotropes, although present in the pars tuberalis, were no longer demonstrable in the pars distalis 3 weeks after stalk section. These results show remarkable agreement between endocrine studies and morphological observations, and indicate a variable degree of dependency of the various pituitary cells on central nervous system influences.

Adrenocorticotropic Hormone↗

Effects of substance P on anterior pituitary secretion in the female rhesus monkey.

The effects of substance P on anterior pituitary secretion were studied in 3 female rhesus monkeys. In nine experiments, 100 microgram substance P was injected intraventricularly, and the results were compared to those obtained following intraventricular injection of the control vehicle. In 7 out of 9 experiments, substance P induced a significant increase in prolactin secretion within 5 min. Peak levels at 10 min were approximately 15-20 times those of the baseline control. Substance P also induced a slight but significant decrease in GH secretion 20 min following injection, but at other times GH levels were not significantly changed. LH and FSH as well as cortisol concentrations remained unaltered. In 2 monkeys a decrease in systolic pressure of 40-70 mm Hg within 10-60 sec and lasting 180-300 sec was observed following the administration of substance P but not the control vehicle. The results indicate that substance P, which in the monkey has been shown to be associated with hypothalamic regions implicated in the control of anterior pituitary secretion, can alter prolactin and GH release.

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High levels of beta-endorphin in hypophyseal portal blood.

beta-Endorphin was measured by RIA in the hypophyseal portal blood of six pig tailed monkeys after pituitary stalk section. The mean beta-endorphin concentration was 4,770 pg/ml (range, 2,900-10,500 pg/ml). This was more than 100 times greater than the mean simultaneous peripheral venous concentration, which was less than or equal to 45 pg/ml. After gel filtration of the portal plasma extracts, the majority of beta-endorphin immunoactivity eluted as a single peak coincident with synthetic beta-endorphin standard. The demonstration of high levels of beta-endorphin in the hypophyseal portal blood suggests that endogenous opioids of hypothalamic origin are secreted into the portal blood and may directly affect the pituitary.

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Effect of estrogen on thyrotropin-releasing hormone-induced release of prolactin in intact, ovariectomized, and stalk-sectioned female rhesus monkeys.

The effects of estrogen treatment on basal and TRH-induced serum PRL concentrations were studied in three groups of four female rhesus monkeys; intact monkeys, ovariectomized animals, and monkeys in which the pituitary gland had been isolated from direct hypothalamic influences by pituitary stalk section. The TRH tests (50 microgram, iv) were performed before and 7 and 21 days after the sc implantation of one or two 3-cm long silastic capsules containing 17 beta-estradiol. Treatment with estradiol significantly increased the PRL response to TRH in the three groups of animals. The highest PRL response to TRH was observed after stalk section. The estrogen treatment also increased basal PRL concentrations in stalk-sectioned monkeys but no statistically significant increase was observed in intact or ovariectomized animals. These results indicate that physiological amounts of estradiol increase the magnitude of TRH-induced PRL release in rhesus monkeys, and that this estrogen effect is probably enacted directly at the level of the anterior pituitary gland.

Animals↗

Failure of beta-endorphin to stimulate prolactin release in the pituitary stalk-sectioned monkey.

To study the locus at which opioids act to release PRL in vivo, beta-endorphin (beta-EP) was injected into intact and pituitary stalk-sectioned monkeys. In each of five intact monkeys, serum PRL rose to peak concentrations of 200-300% of baseline 20 min after injection. In contrast, beta-EP failed to cause any PRL increase in four stalk-sectioned animals. Beta-EP also failed to stimulate PRL in two stalk-sectioned monkeys receiving estrogen replacement, indicating that estrogen deficiency was not the cause of their failure to respond. To test possible antagonism of dopamine by beta-EP directly at the pituitary, L-dopa was given to six stalk-sectioned monkeys with and without beta-EP pretreatment. No alteration of the PRL suppression by L-dopa was observed Disappearance of injected beta-EP from plasma was studied in four intact monkeys. Initial and terminal half-lives ranged from 2.3-4.0 min and from 16.0-30.2 min, respectively; MCRs ranged from 70-170 ml/min. We conclude that beta-EP does not stimulate PRL secretion either directly or by interacting with dopamine at the pituitary level. These results support a hypothalamic rather than a direct pituitary site of action for opioid-stimulated PRL release.

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The effects of serotonin on prolactin and growth hormone concentrations in normal and pituitary stalk-sectioned monkeys.

The effects of serotonin on PRL and GH secretion were studied in normal and pituitary stalk-sectioned female rhesus monkeys. Serotonin was administered iv at doses of 50, 500, 5000 microgram. Pretreatment concentrations of serum PRL were elevated in stalk-sectioned monkeys compared to normal monkeys [34 +/- 5 vs. 3 +/- 1 ng/ml (mean +/- SEM)], while serum GH concentrations were lower in the stalk-sectioned animals (< 0.5 vs. 1.3 +/- 0.2 ng/ml). In both normal and stalk-sectioned monkeys, the 5-microgram dose of serotonin failed to alter PRL concentrations. However, with the 500-microgram dose, PRL rose from 3 +/- 1 to 22 +/- 6 ng/ml in normal monkeys and from 27 +/- 6 to 57 +/- 10 ng/ml in stalk-sectioned monkeys. Likewise, with the 5000-microgram dose, PRL rose from 4 +/- 2 to 82 +/- 27 and from 30 +/- 6 to 75 +/- 26 ng/ml in the two respective groups. No dose of serotonin stimulated GH secretion in stalk-sectioned monkeys, although GH did increase from approximately 2 to 4-11 ng/ml in normal monkeys. Since the pituitary is devoid of direct hypothalamic influences in the pituitary stalk-sectioned animals, these results suggest that serotonin can modulate PRL secretion either directly at the pituitary level or via some yet to be determined peripheral mechanism. In contrast, this neurotransmitter appears to incorporate hypothalamic factors in its modulation of GH secretion.

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Immunocytochemical distribution of corticotropin (ACTH) in monkey brain.

The distribution of adrenocorticotropin (ACTH) in monkey brain was examined by immunoperoxidase immunohistochemistry. An antiserum to ACTH that recognized the C-terminal portion of the molecule was used. Immunoreactive ACTH was visualized as an intraneuronal constituent with a widespread distribution throughout the brain. Reactive cell bodies were seen only in the region of the arcuate nucleus of the hypothalamus. Dense axonal networks were seen in the hypothalamus, mesencephalic gray, and in the region around the anterior commissure. No staining was seen in the cerebral cortex, cerebellum, hippocampus, or striatum. ACTH or fragments of ACTH may function as neurotransmitters or neuromodulators in primate brain.

Adrenocorticotropic Hormone↗

The pars tuberalis of the rhesus monkey secretes luteinizing hormone.

The presence of luteinizing hormone within the pars tuberalis of the adenohypophysis and its secretion into pituitary stalk vessels were investigated in adult rhesus monkeys. Portal blood was collected in 9 monkeys, after section of the pituitary stalk. In 22 out of 26 samples, portal to peripheral LH ratios, as measured by radioimmunoassay, ranged from 2 to 48. Portal LH levels were highest in 3 animals studied at the time of the midcycle surge. No differences between portal and peripheral growth hormone (GH) and prolactin levels were observed. Immunocytochemical studies in 4 normal and 3 ovariectomized female monkeys indicated that LH, but not GH, prolactin or thyroid stimulating hormone were present within the pars tuberalis. Cells containing these hormones were identified within the pars distalis. These results indicate that the pars tuberalis forms and secretes LH via the hypophyseal portal circulation.

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Regeneration of the magnocellular system of the rhesus monkey following hypothalamic lesions.

The hypothalamic magnocellular system of the rhesus monkey was studied with specific immunocytochemical techniques in animals that had undergone hypothalamic lesions. The results indicate that this system maintains a regenerative capacity even when its tracts are interrupted within the hypothalamus. New neurohemal units are reconstituted from newly formed vessels within the scar as well as from preexistent blood vessels, such as perforating and pial arterioles, and the vessels of the pars tuberalis of the pituitary gland, which normally do not contain neurosecretory terminals.

Animals↗