In an attempt to determine whether prolactin influences estrogen biosynthesis in the ovary, the estrogenic responses of women with amenorrhea under treatment with human menopausal gonadotropin (hMG), with and without the simultaneous administration of the prolactin inhibitor bromocriptine, were investigated in a total of 20 treatment cycles. In five of the six women studied, the addition of bromocriptine produced a urinary excretion of estrogenic compounds 79% higher than that produced by treatment with hMG alone. In one woman with a slightly increased serum prolactin level, the addition of bromocriptine necessitated halving the total hMG dosage. One woman with low endogenous levels of follicle-stimulating hormone (FSH) and a limited response to gonadotropin-releasing hormone showed no increased estrogen excretion after bromocriptine administration over that produced by hMG alone. These results suggest that (1) both elevated and normal serum prolactin levels can have a direct inhibitory effect on the ovary and (2) FSH may be necessary for the formation of prolactin receptors in the ovary.
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The STH level was studied in the blood of 105 patients with the hypothalamic pubertal syndrome (HPS). A tendency toward STH hyperproduction was revealed. A comparison of the STH level in the blood and the degree of obesity of the HPS patients showed a clear decrease of the growth hormone in Stage IV obesity. The STH level was almost the same in Stages I, II, III obesity. The STH secretion in the HPS patients correlated with age. The period of disease did not influence hypophysial somatotropic function in the HPS patients. No interrelationship between the content of hydrocortisone and STH in the blood was established. In most of the patients with the HPS, the growth hormone secretion in response to hypoglycemia was undisturbed. Preliminary results obtained with parlodel tests showed an opposite reaction in the HPS patients as compared to healthy ones. Our results confirmed once more that the HPS should not be interpreted as a variant of Icenko-Cushing's syndrome or constitutional obesity in which STH production was lowered.
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The mechanism of the antihypertensive properties of bromocriptine was investigated in dog and man. In anaesthetized dogs, bromocriptine induced a decrease in the pressor responses to adrenaline or phenylephrine and reduced the hypotensive properties of clonidine. In 6 hypertensive patients with Parkinson's disease, chronic treatment with bromocriptine (46.4 +/- 12.0 mg/day) elicited both a significant decrease in blood pressure and an improvement of extrapyramidal symptoms. During bromocriptine therapy, domperidone (60 mg/day during 1 month), a specific peripheral dopaminergic antagonist was introduced. The drug did not change the levels of blood pressure (before domperidone: 150.8 +/- 22.5/79.9 +/- 8.9 mmHg after domperidone: 150 +/- 17.3/87.5 +/- 12.9 mmHg). These results confirm the antihypertensive properties of bromocriptine and demonstrate that, beside their dopaminergic properties, the drug also possesses mixed alpha 1 and alpha 2 adrenolytic actions. These two properties may contribute to the mechanism of the antihypertensive effects of bromocriptine. These data also show that domperidone can be used in bromocriptine-treated hypertensive parkinsonians without side effects on blood pressure.
Forty-two patients with elevated serum prolactin were treated in a randomized, open-label trial with the conventional ergot bromocriptine, or a new ergot pergolide. Before treatment, the patients underwent thorough endocrine evaluation and computed tomographic scan. All patients had prolactin levels greater than 25 ng/ml, and 27 patients had a pituitary mass. Follow-up studies performed after 6 months of treatment showed both drugs effectively reduced prolactin levels to normal, though pergolide effects were more rapid. There was no change in the contents of the pituitary fossa in the 10 patients with hyperprolactinemia but without pituitary mass. Sixty percent of patients with pituitary mass had diminution of tumor size. Pergolide appears to be an effective medical treatment for hyperprolactinemia and pituitary tumor and offers a possible alternative to bromocriptine and surgical treatment.
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The neuromodulator acetylcholine (ACh) modulates spatial integration in visual cortex by altering the balance of inputs that generate neuronal receptive fields. These cholinergic effects may provide a neurobiological mechanism underlying the modulation of visual representations by visual spatial attention. However, the consequences of cholinergic enhancement on visuospatial perception in humans are unknown. We conducted two experiments to test whether enhancing cholinergic signaling selectively alters perceptual measures of visuospatial interactions in human subjects. In Experiment 1, a double-blind placebo-controlled pharmacology study, we measured how flanking distractors influenced detection of a small contrast decrement of a peripheral target, as a function of target/flanker distance. We found that cholinergic enhancement with the cholinesterase inhibitor donepezil improved target detection, and modeling suggested that this was mainly due to a narrowing of the extent of facilitatory perceptual spatial interactions. In Experiment 2, we tested whether these effects were selective to the cholinergic system or would also be observed following enhancements of related neuromodulators dopamine (DA) or norepinephrine (NE). Unlike cholinergic enhancement, DA (bromocriptine) and NE (guanfacine) manipulations did not improve performance or systematically alter the spatial profile of perceptual interactions between targets and distractors. These findings reveal mechanisms by which cholinergic signaling influences visual spatial interactions in perception and improves processing of a visual target among distractors - effects that are notably similar to those of spatial selective attention.Significance StatementAcetylcholine influences how visual cortical neurons integrate signals across space - perhaps providing a neurobiological mechanism for the effects of visual selective attention. However, the influence of cholinergic enhancement on visuospatial perception remains unknown. Here we demonstrate that cholinergic enhancement improves detection of a target flanked by distractors, consistent with sharpened visuospatial perceptual representations. Furthermore, while most pharmacological studies focus on a single neurotransmitter, many neuromodulators can have related effects on cognition and perception. Thus, we also demonstrate that enhancing noradrenergic and dopaminergic systems does not systematically improve visuospatial perception or alter its tuning. Our results link visuospatial tuning effects of acetylcholine at the neuronal and perceptual levels and provide insights into the connection between cholinergic signaling and visual attention.
The morphological effect of chronic synthetic and secretory inhibition of the intermediate lobe of the rat pituitary induced by bromocriptine treatment was studied using morphometric techniques in combination with electron microscopy. On the basis of granule diameters, a heterogeneous cell population was shown in the normal intermediate lobe. Bromocriptine treatment did not induce any change in the volume fraction, number or location of electron-dense secretory granules. Instead, there was a shift toward a more homogeneous cell population containing smaller granules, the mean granule volume being reduced by approximately 30%. The volume fraction of electron-lucent granules or vacuoles was markedly reduced, indicating a functional significance of these organelles. The volume of the Golgi apparatus was not significantly altered, but the number of condensing granules within the Golgi area was reduced. The volume of the intermediate lobe was decreased, apparently due to a decrease in the mean cell volume.
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We studied secretion of growth hormone (GH), insulin, and prolactin in eight women with anorexia nervosa and nine women with refractory obesity before and during treatment with bromocriptine, 10 mg/day. In the anorexic patients the raised plasma GH concentrations occurring during an oral glucose tolerance test fell significantly while on bromocriptine treatment, but there was no change in plasma insulin or blood glucose concentrations. In the obese patients, however, plasma GH concentrations remained low during the oral glucose tolerance test, and were not modified by bromocriptine. Blood glucose and plasma insulin concentrations were also unchanged. Plasma GH and plasma 11-hydroxycorticosteroid responses to insulin-induced hypoglycaemia were unaffected. Serum prolactin concentrations which were raised in five anorexic patients and marginally raised in two obese subjects, fell significantly in both groups during treatment. We observed no consistent weight changes in either groups.
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The influence of prolactin (PRL) on the development of the immune system in the mouse was studied by injecting mothers with bromocriptine (CB-154) to produce hypoprolactinemic milk. Alterations in pup thymocyte and splenocyte cell subsets were observed to graded doses of CB-154 administered to mothers. There was an increase in the relative percentages of neonate thymic CD4 and CD8 cells at 5 days of age when mothers were injected with 100 micrograms of CB-154 2 x daily from day 1 to 5 of lactation, however, there was no alteration in absolute thymic subset cell numbers. The relative percentage of pup spleen CD4, CD8 and B cells were increased when mothers were administered 50 or 100 micrograms of CB-154 and the 50 micrograms dose resulted in a significant increase in the absolute number of CD4 cells while the 100 micrograms dose induced a significant decrease in the three splenic cell subsets examined. Graded doses of CB-154 administered to mothers resulted in decreases in the PRL concentration of stomach milk as measured by the Nb2 cell proliferation assay. The serum PRL level of the pups, however, was not altered by any dose of CB-154 injected to the mothers. The administration of PRL to pups nursing mothers given the 100 micrograms dose of CB-154 did not alter the pup thymocyte and splenocyte subset population from that of litter-mate controls. The administration of mouse PRL and mouse growth hormone antisera to pups nursing saline-injected mothers did not alter thymocyte and splenocyte subsets from that of saline-injected litter mate controls. The proliferation of neonatal thymocytes by Con-A stimulation was not altered by CB-154 injection to mothers and PRL administration to pups. However, since the percentage of thymic CD4 and CD8 cells in the thymus was increased 2 to 3 fold, the apparent lack of effect was in fact a decrease in the responsiveness of the thymocytes. Con-A stimulation of neonatal splenocytes resulted in a significant increase in proliferation for mothers administered CB-154 in keeping with the increase relative percentage of CD4 and CD8 cells observed. Prolactin administration to the pups did not alter the response. LPS stimulation of neonatal splenocytes increased the proliferation of B cells taken from pup nursing mothers administered CB-154 and PRL administration appeared to partially block this proliferation.(ABSTRACT TRUNCATED AT 400 WORDS)
During early life, prolactin (PRL) ingested by the pups through the milk participates in the development of neuroendocrine, immunological and reproductive systems. The present study tested whether a deficiency in PRL in the dam's milk during early lactation affected the offspring in terms of the maternal responsiveness in the sensitization paradigm and behavioral response to a novel environment in the offspring. Thus, lactating rats were injected (sc) on postnatal days (PND) 2-5 with bromocriptine (125 microg/day), bromocriptine+ovine PRL (125 microg+300 microg/day), or vehicle. As juveniles (at PND 24) or adults (PND 90-100), one female from each litter was exposed to 5 foster pups continuously for 8 days and their maternal responsiveness was recorded. Female offspring were also tested in an open field arena. Adult, but not juvenile, female offspring of bromocriptine-treated mothers showed an increased latency to become maternal, in comparison to latencies displayed by the offspring of control mothers. Furthermore, the proportion of adult, but not juvenile, offspring of bromocriptine-treated mothers that became maternal was lower than that showed by the offspring of vehicle-treated mothers. In comparison to female offspring of vehicle-treated mothers, female offspring of bromocriptine-treated mothers spent less time hovering over the pups (as juvenile females), body licking (as both juvenile and adult females), and in close proximity to pups (as adult females) during the maternal behavior test. Simultaneous administration of ovine PRL and bromocriptine reversed almost all the negative effects of bromocriptine. These data suggest that maternally-derived PRL participates during the early postnatal period in the development of neural systems that underlie the control of maternal behavior.
Cabergoline should be first-line therapy for aggressive prolactinomas, even in those patients who present with visual field defects.
The influence of 2-bromo-alpha-ergocryptine (CB-154) and 2-chloro-6-methyl-ergoline-8beta-acetonitrile methanesulfonate (lergotrile mesylate) on prolactin (PRL) and growth hormone (GH) secretion in mice was investigated. Both drugs inhibited the nursing-induced rise in serum PRL in lactating mice, CB-154 being effective at a somewhat lower dosage than lergotrile mesylate. Both drugs reduced basal concentrations of serum PRL by more than 90% within an hr after administration, but the effect of CB-154 lasted for several hr longer than that of lergotrile mesylate. CB-154 did not change the resting concentrations of GH in mice, but it promoted the induction of GH release by nursing; injection of lergotrile mesylate, on the other hand, seemed to enhance the basal concentrations of GH in lactating mice that were separated from their young for 12 hr. The results show that both drugs can be used successfully for reducing PRL secretion in the mouse.