Modulation of postinhibitory rebound rise in plasma GH by hypothalamic hormones in patients with acromegaly

To evaluate the GH regulating mechanism in acromegalic patients, post-inhibitory rebound rise in GH secretion induced by somatostatin was studied in these cases and normal subjects, and was compared with the rebound GH rise induced by dopamine. After somatostatin infusion (500 micrograms/75 min) both 5 normal and 9 acromegalic subjects showed prompt GH decreases during the infusion (% decrease: 69.1 +/- 10.4 vs 74.4 +/- 5.1) and showed rebound rises after its termination. However, the rebound rises occurred more promptly and markedly in normal controls than in acromegalic patients, i.e. the rebound peak appeared at 45 min in normal controls and at 75 min in acromegalic patients after the cessation of somatostatin infusion. Dopamine (DA) infusion (5 micrograms/kg/min for 90 min) also induced similar inhibition and postinhibitory rebound rises in GH secretion in 7 patients with acromegaly. Although the maximum inhibition (65.6 +/- 6.4% vs 74.4 +/- 5.1%) and the inhibitory area (4338.0 +/- 481.5% X min vs 3682.5 +/- 295.5% X min) during the DA or somatostatin infusion were not different, the rebound at 15 min was significantly greater after DA than after somatostatin (p less than 0.02). When TRH was injected at the termination of somatostatin infusion, the rebound increase was significantly enhanced and the rebound peak appeared 45 min earlier than after a single somatostatin administration. Similarly, hp GRF (1-44)-NH2 enhanced the postinhibitory rebound rises in 4 patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Catecholamines and pituitary function. III. Restoration of the prolactin response to thyrotropin-releasing hormone by low-dose dopamine infusion in women with pathological hyperprolactinemia

Previous studies in Rhesus monkeys have demonstrated that a dopamine (DA) infusion rate of 0.1 microgram/kg X min induces peripheral DA levels similar to those measured in hypophysial stalk blood and normalizes serum prolactin (PRL) levels in stalk-transected animals. We therefore examined the effect of such DA infusion rate on basal and thyrotropin-releasing hormone (TRH)-stimulated PRL secretion in both normal cycling women and women with pathological hyperprolactinemia. 0.1 microgram/kg X min DA infusion fully normalized PRL serum levels in 8 normal cycling women whose endogenous catecholamine synthesis had been inhibited by alpha-methyl-p-tyrosine (AMPT) pretreatment. Furthermore, DA significantly reduced, but did not abolish, the rise in serum PRL concentrations induced by both acute 500 mg AMPT administration and 200 micrograms intravenous TRH injection in normal women. A significant reduction in serum PRL levels in response to 0.1 microgram/kg X min DA, similar to that observed in normal cycling women when expressed as a percentage of baseline PRL, was documented in 13 amenorrheic patients with TRH-unresponsive pathological hyperprolactinemia. However, a marked rise was observed in the serum PRL of the same patients when TRH was administered during the course of a 0.1-microgram/kg X min DA infusion. The PRL response to TRH was significantly higher during DA than in basal conditions in hyperprolactinemic patients, irrespective of whether this was expressed as an absolute increase (delta PRL 94.4 +/- 14.2 vs. 17.8 +/- 14.1 ng/ml, p less than 0.002) or a percent increase (delta% PRL 155.4 +/- 18.9 vs. 17.9 +/- 7.1, p less than 0.0005), and there was a significant linear correlation between the PRL decrements induced by DA and the subsequent PRL responses to TRH. These data would seem to show that the 0.1-microgram/kg X min DA infusion rate reduces basal PRL secretion and blunts, but does not abolish, the PRL response to both TRH and acute AMPT administration. The strong reduction in PRL secretion and the restoration of the PRL response to TRH by 0.1 microgram/kg X min DA infusion in high majority of hyperprolactinemic patients, seem to indicate that both PRL hypersecretion and abnormal PRL response to TRH in women with pathological hyperprolactinemia are due to a relative DA deficiency at the DA receptor site of the pituitary lactotrophs.     

Catecholamines and pituitary function. VI. Effect of different dopamine doses on TRH-induced prolactin release in women with pathological hyperprolactinemia

The present study was designed to examine the effect of low-dose dopamine (DA) infusion rates (0.02 and 0.1 microgram/kg X min) on both basal and TRH-stimulated prolactin release in normal and hyperprolactinemic individuals. Sixteen normally menstruating women in the early follicular phase of a cycle and 23 hyperprolactinemic patients were studied. 0.1 microgram/kg X min DA was infused in 8 normal women and 15 patients with pathological hyperprolactinemia, while 8 normal controls and 8 patients received 0.02 microgram/kg X min DA TRH (200 micrograms, i.v.) was administered alone and at the 180th min of the 5-hour DA infusion in all controls and patients. A significant reduction in serum PRL levels, which was similar in normal women (-59.5 +/- 4.0%, mean +/- SE) and hyperprolactinemic patients (-48.2 +/- 5.5) was observed in response to 0.1 microgram/kg X min DA. In normal cycling women DA infusion significantly (P less than 0.02) reduced the PRL response to TRH with respect to the basal TRH test (delta PRL 45.0 +/- 7.0 vs. 77.9 +/- 15.4 ng/ml). On the contrary, the PRL response to TRH was significantly higher during 0.1 microgram/kg X min DA than in basal conditions in hyperprolactinemic patients, both in absolute (delta PRL 91.8 +/- 17.6 vs. 38.4 +/- 6.8, P less than 0.03) and per cent (198.5 +/- 67.6 vs. 32.1 +/- 7.5, P less than 0.02) values. A normal PRL response to TRH, arbitrarily defined as an increase greater than 100% of baseline, was restored in 11 out of 15 previously unresponsive hyperprolactinemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Possible thyrotrophs insensitivity to dopamine in hyperprolactinaemic amenorrhoeic patients

The study assessed the sensitivity of the thyrotrophs of hyperprolactinaemic patients to a physiological dose of dopamine (DA). Eight hyperprolactinaemic amenorrhoeic patients received 4-hour infusions of either DA (0.4 micrograms/kg x min) or glucose. Twelve normal women served as controls. In normal women the mean thyrotrophin (TSH) concentration declined significantly (P less than 0.05) from 81 +/- 6.6% of basal levels during glucose infusion to 59 +/- 5.8% of basal levels during DA infusion. In contrast DA infusion to hyperprolactinaemic patients caused no significant reduction in TSH levels compared to glucose infusion (DA infusion 68 +/- 4.7% of basal levels; glucose infusion 73 +/- 4.9% of basal levels). DA infusion caused a significant reduction in serum prolactin (PRL) levels both in hyperprolactinaemic patients (P less than 0.001) and normal women (P less than 0.02), but the PRL suppression was significantly (P less than 0.05) less pronounced in the hyperprolactinaemic patients, compared to normal women. We propose that the abnormal PRL as well as TSH secretion in hyperprolactinaemic amenorrhoeic patients may be due to a common defect. Both the lactotrophs and the thyrotrophs may be relatively insensitive to dopaminergic inhibition.     

Zinc: an inhibitor of prolactin (PRL) secretion in humans

The response of plasma prolactin (PRL) to oral administration of increasing doses of zinc (25.0, 37.5 and 50.0 mg) was studied in 17 normal adult men and women. Blood samples were collected at 10 and 30-min intervals over a period of 120 min after two basal times (-30 and 0 min). PRL concentrations significantly fell below basal levels in all subjects in response to the increase in plasma zinc levels, as compared to the controls. These results suggest that acute hyperzincemia can inhibit basal PRL secretion in normal individuals.     

Catecholamines and pituitary function. VII: Effects of acute and chronic dopamine-receptor blockade on pituitary response to TRH-GNRH in normal women and in patients with hyperprolactinemic amenorrhea

To investigate whether an enhanced dopamine (DA) inhibition on pituitary thyrotrophs and gonadotrophs may account for the abnormal TSH and LH dynamics in pathological hyperprolactinemia, we examined the effect of an acute lysis of the putative DA overinhibition, as obtained with continuous domperidone (DOM) infusion, on both basal and TRH-GnRH stimulated PRL, TSH and LH release in both normal cycling women and patients with pathological hyperprolactinemia. The effect of TRH-GnRH administration was also examined in women with DA-antagonist induced hyperprolactinemia, in order to evaluate the effect of a chronic lack of the physiological DA inhibition on pituitary hormone dynamics. Patients with both pathological and DA-antagonist induced hyperprolactinemia displayed an evident TSH and LH hyper-responsiveness to TRH-GnRH. The PRL response was reduced in the former but enhanced in the latter group. Domperidone infusion resulted in a marked increase in serum PRL levels in normal cycling women, but not in patients with pathological hyperprolactinemia. The abolition of the putative DA-overinhibition at the pituitary level with DOM infusion in patients with pathological hyperprolactinemia was followed by a slight increase in basal TSH output but did not modify the TSH and LH hyperresponsiveness to TRH-GnRH. The similarities in TSH and LH dynamics between patients with pathological and DA-antagonist induced hyperprolactinemia and the ineffectiveness of DOM infusion in modifying the TSH and LH hyper-responses to TRH-GnRH in the former group, seem to exclude the widely accepted idea that endogenous DA overactivity is responsible for the abnormal thyrotroph and lactotroph dynamics in women with hyperprolactinemic amenorrhea.     

Prolactin after baclofen in healthy subjects and prolactinoma patients

Serum prolactin (PRL) levels in basal conditions (two samples) and 30, 60, 90, 120, 150 e 180 minutes after oral administration of baclofen (20 mg) were evaluated in 6 healthy subjects and in 10 patients with prolactinoma. The effect of baclofen (20 mg by mouth) on the PRL secretion cimetidine (400 mg i.v.) or domperidone (20 mg i.v.) induced were evaluated in 9 healthy women by administration of baclofen 60 minutes before cimetidine or domperidone. Baclofen was unable to significantly rise serum PRL levels in healthy subjects and in patients affected by prolactinoma and furthermore did not interfere with PRL rise domperidone induced. On the contrary baclofen decreased PRL rise cimetidine induced. It was concluded that: in basal condition, GABAb receptor don't play an obvious role in modulation of PRL secretion; when H2 istaminergic inhibition on PRL secretion is blocked (at an hypothalamic site), a GABA inhibition, b receptor mediated, on PRL secretion became more clear; the domperidone blockade of hypophysial dopaminergic receptors suggests that GABAb modulation of prolactin secretion don't obtain itself by dopaminergic pathways.     

Prolactin secretion in patients with idiopathic diabetes insipidus.

It has been demonstrated that hyperprolactinemia is sometimes present even in patients with idiopathic diabetes insipidus (DI). In this study, we examined the responses of serum prolactin (PRL) to hypertonic saline infusion and TRH injection in 11 patients with idiopathic DI diagnosed by clinical examinations. Serum sodium in these patients (147.5 +/- 3.2 mEq/L) was significantly higher at baseline than in normal subjects (139.7 +/- 2.4 mEq/L). The plasma arginine vasopressin (AVP) level was significantly lower in DI (0.42 +/- 0.24 pg/ml) at baseline than in normal subjects (2.53 +/- 1.03 pg/ml). However, the serum PRL level in both groups did not differ significantly except in one patient with idiopathic DI (35.6 ng/ml). There was no significant correlation between the basal serum sodium and basal serum PRL in either group. After an infusion of hypertonic saline, the serum sodium level gradually increased to 155.6 +/- 3.4 mEq/L in DI and to 146.5 +/- 4.3 mEq/L in the normal subjects. However, this increase did not affect PRL secretion in either group. PRL response to TRH was essentially normal in all patients with idiopathic DI. These results indicate that the secretion of PRL is not generally affected by chronic mild hypernatremic hypovolemia in the patients with idiopathic DI.     

血管活性肠肽对清醒大鼠催乳素分泌的影响

在离体研究中发现,血管活性肠肽（ＶＩＰ）对催乳素分泌的促进作用因垂体所取自的动物模型的不同而异。本实验则以不同生理状态的大鼠为动物模型,于清醒自由活动状态下,检验ＶＩＰ的静脉注入对催乳素释放的影响。结果表明,在ＶＩＰ注入后１０ｍｉｎ时,其外周血液的浓度达到最高值（２１３２±２３３）ｎｇ／ｍｌ,并至少持续３０ｍｉｎ。在本实验的所有动物模型中,ＶＩＰ均诱导出了显著的催乳素分泌峰（Ｐ＜００５）,就其提高程度而言,雄性鼠最高（１５８０４±３７０６）ｎｇ／ｍｌ,未经吸吮刺激的哺乳母鼠最低（３１０５±４４２）ｎｇ／ｍｌ,而经过吸吮刺激的哺乳母鼠则居于两者之间（９０１０±３６００）ｎｇ／ｍｌ。ＶＩＰ在不同动物模型中所表现出的这些差异,提示其作用方式和／或作用部位可能受到整个机体内分泌环境和神经刺激的整合。     

Growth hormone and prolactin secretion after metoclopramide administration (DA2 receptor blockade) in fertile women.

In this report, we will describe the results of a cross-sectional study to assess PRL and GH secretion during the early follicular phase in 22 fertile patients after metoclopramide administration in order to achieve a dopaminergic DA2 receptor blockade. Blood samples were collected at - 15, 0, 15, 30, 45 and 60 minutes. PRL, GH, estradiol, IGF-I, TSH, glucose, and insulin were measured in the samples taken at - 15 and 0 minutes. The existence of a correlation between GH and PRL secretion was investigated. All patients presented normal serum levels of estradiol, prolactin, insulin, fasting glucose and IGF-I. Serum GH levels were not changed after metoclopramide infusion (p = 0.302), but there was a significant alteration in serum PRL (p = 0.0001) with the highest levels after 30 (mean: 237.20 ng/ml +/- 95.86) and 45 (mean: 211.80 ng/ml +/- 83.24) minutes. Serum GH levels did not correlate with serum PRL levels after the dopaminergic DA2 blockade. We conclude that GH secretion was not modulated by a direct effect of type 2 dopamine receptor.     

Effect of [D-Trp6]LHRH infusion on prolactin secretion by perifused rat pituitary cells

The effect of a superactive agonistic analog of luteinizing hormone-releasing hormone (LHRH), [D-Trp6]LHRH on prolactin (PRL) secretion by perifused rat pituitary cells was investigated. Constant infusion of [D-Trp6]LHRH (0.5 ng/min) for 2-3 h elicited a significant decrease in PRL secretion by these cells. This decrease in PRL release started ca. 30 min after the beginning of the infusion with the LHRH analog and lasted up to 1.5-2 h. [D-Trp6]LHRH significantly stimulated luteinizing hormone (LH) secretion during the first 30 min of peptide infusion; thereafter, LH levels began to return to control values. In animals pretreated in vivo with 50 micrograms of [D-Trp6]LHRH (s.c.) 1 h before sacrifice, PRL secretion by the rat pituitary cell perifusion system was significantly lower than vehicle-injected controls throughout the entire [D-Trp6]LHRH infusion period. On the other hand, thyrotropin-releasing hormone (TRH)-stimulated PRL secretion was slightly, but significantly imparied by [D-Trp6]LHRH infusion, while dopamine (DA) inhibition of PRL release was unaffected by this same treatment. These results reinforce previous observations of a modulatory effect of [D-Trp6]LHRH, probably mediated by pituitary gonadotrophs, on PRL secretion by the anterior pituitary. In addition, our findings suggest that basal PRL secretion by the lactotroph may be dependent on a normal function of the gonadotroph. The collected data from this and previous reports support the existence of a functional link between gonadotrophs and lactotrophs in the rat pituitary gland.     

Possible direct effect of serotonin on pituitary prolactin secretion: in vivo and in vitro studies

In this work we analyze the possibility of serotonin (5-HT)-releasing prolactin (PRL) through a direct action at the pituitary level. 5-HT (2 mg/kg i.v.) stimulates PRL secretion in hypophysectomized autotransplanted animals (HAG) significantly and this effect was not influenced by pretreatment with the dopaminergic antagonist domperidone. In perifused pituitaries, 5-HT administration (0.01, 0.1 and 1 microM for 90 min, or 1, 10, 100 microM for 15 min) was ineffective in stimulating PRL release. In pituitaries obtained from animals previously treated with the neurotoxic 5,7-dihydroxytryptamine (5,7-DHT) or vehicle and incubated in the presence of 5-HT (2.5, 5 and 10 microM), no response in PRL secretion was observed. These results suggested that 5-HT does not release PRL through a direct pituitary action, and that the effect observed in HAG animals could be mediated through the release of a PRL-releasing factor after 5-HT administration.     

A comparison of the effects of suckling or transient dopamine antagonism on thyrotropin-releasing hormone and suckling induced prolactin release in lactating rats

Prolactin (PRL) release was studied in mid-lactational female rats by comparing the stimulatory influence of suckling to a drug protocol that mimics the effect of suckling on the anterior pituitary (AP). Animals that nursed pups for 15 minutes and were allowed to suckle again 60 minutes later for 10 minutes, released PRL effectively during both nursing episodes; however, in animals that received the dopamine (DA) agonist 2-Br-alpha-ergocryptine maleate (CB-154, 0.5 mg/rat i.v.) at the end of the first nursing period did not show an increase in plasma PRL to a second suckling stimulation by the pups. When thyrotropin releasing hormone (TRH) was substituted for the second suckling period in CB-154 treated rats, a slight increase in plasma PRL occurred 5 minutes after the injection. In a third study we transiently blocked the action of DA at the AP by injecting the DA antagonist domperidone (0.01 mg/rat i.v.), followed 5 minutes later by the administration of CB-154. One hour later animals were either allowed to suckle pups for 10 minutes or were injected with TRH. Treatment with TRH resulted in an 11 fold increase in plasma PRL but suckling was completely ineffective in inducing PRL release. These data suggest that the lack of PRL release to suckling in CB-154 treated rats was due to inhibitory effects of CB-154 on neural mechanisms which link nursing to PRL release. In addition, the data show that pharmacologic DA antagonism affects TRH releasable PRL more than does suckling. This may be due to a reduction, by suckling, of the pool of PRL that is available to be released by TRH administration.     

Involvement of hypothalamic dopamine in the regulation of prolactin secretion

The neuroendocrine control of prolactin (PRL) secretion is known to be a multifactorial process, but dopamine (DA) secreted by the tuberoinfundibular dopaminergic (TIDA) neurons of the hypothalamus is believed to exert a predominant inhibitory control on the secretion of PRL. The secretory activity of the TIDA neurons, including the rate of biosynthesis of DA and the rate of release of the neurohormone into hypophysial portal blood, can be readily evaluated in the rat. In most conditions in which an altered secretion of PRL has been documented, an altered secretory activity of the TIDA neurons has been found. When an acute reduction in the secretion of DA is observed, an increased secretion of PRL is associated, with an inverse relationship between DA and PRL concentrations in hypophysial portal and systemic blood, respectively. However, the secretion of PRL can be regulated by PRL itself through stimulation of the secretory activity of the TIDA neurons, and consequently hyperprolactinemia can be observed concomitantly with a sustained high secretion of DA, as seen after treatment with estrogen. The short loop feedback of PRL secretion seems to be impaired in the aging rat, since a sustained reduced hypothalamic secretion of DA is observed in spite of long-term hyperprolactinemia.     

Reproductive experience modifies dopaminergic function, serum levels of prolactin, and macrophage activity in female rats

Reproductive experience (RE), i.e. pregnancy and lactation, induces physiological changes in mammals. Recent data show that neuroimmune interactions are modulated by a diversity of events involving neurotransmitters and neuropeptides. These molecules, particularly dopamine (DA), were reported to mediate the relevant cross talk between immune and neuroendocrine systems. Moreover, DA-mediated regulation of leukocyte function is a reasonable approach to investigate the DA-operated regulatory switch for immune-competent cells, such as macrophages. Therefore, the goals of the present study were to determine the effects of RE on: (1) dopaminergic function through hypothalamic levels of DA, dihydroxyphenylacetic acid (DOPAC), homovanilic acid (HVA), serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA); (2) basal levels of circulating prolactin (PRL); and (3) activity of peritoneal macrophage (phagocytosis and oxidative burst). A total of 16 adult (200-250 g) female Wistar rats were used, divided in two groups: nulliparous and primiparous. Approximately 2-3 weeks after weaning pups from the primiparous group, both groups of rats were tested. The findings indicate that: (1) DOPAC concentrations, DOPAC/DA and HVA+DOPAC/DA ratios decreased in primiparous rats as compared to virgin rats, (2) primiparous rats showed significantly lower serum PRL levels, and (3) phorbol miristate acetate (PMA)-induced oxidative burst was decreased in peritoneal macrophage from primiparous rats as compared to virgin rats. To test the possible positive correlation between serum levels of PRL and the intensity of oxidative burst by peritoneal macrophage, an extra experiment was done with adult virgin female rats treated with domperidone, an antagonist of DA receptors. Domperidone-treated animals showed increased serum levels of PRL and simultaneous increase in peritoneal macrophage oxidative burst. Thus, suggesting an indirect participation of hyperprolactinemia, induced by this treatment in peritoneal macrophage activity of female rats. These results suggest that a previous RE can modulate the activity of dopaminergic hypothalamic systems, while decreasing PRL serum levels and the oxidative burst of peritoneal macrophage. The neurochemical and hormonal RE-induced changes correlate with the immune alterations.     

Hormonal regulation of prolactin release by human prolactinoma cells cultured in serum-free conditions

Thyrotropin-releasing hormone (TRH) stimulates the prolactin (PRL) release from normal lactotrophs or tumoral cell line GH3. This effect is not observed in many patients with PRL-secreting tumors. We examined in vitro the PRL response to TRH on cultured human PRL-secreting tumor cells (n = 10) maintained on an extracellular matrix in a minimum medium (DME + insulin, transferrin, selenium). Addition of 10(-8) M TRH to 4 X 10(4) cells produced either no stimulation of PRL release (n = 6) or a mild PRL rise of 32 +/- (SE) 11% (n = 4) when measured 1, 2 and 24 h after TRH addition. When tumor cells were preincubated for 24 h with 5 X 10(-11) M bromocriptine, a 47 +/- 4% inhibition of PRL release was obtained. When TRH (10(-8) M) was added, 24 h after bromocriptine, it produced a 85 +/- 25% increase of PRL release (n = 8). This stimulation of PRL release was evident when measured 1 h after TRH addition and persisted for 48 h. The half maximal stimulatory effect of TRH was 2 X 10(-10) M and the maximal effect was achieved at 10(-9) M TRH. When tumor cells were pretreated with various concentrations of triiodothyronine (T3), the PRL release was inhibited by 50% with 5 X 10(-11) M T3 and by 80% with 10(-9) M T3. Successive addition of TRH (10(-8) M) was unable to stimulate PRL release at any concentration of T3. The addition of 10(-8) M estradiol for up to 16 days either stimulated or had no effect upon the PRL basal release according to the cases. In all cases tested (n = 4), preincubation of the tumor cells with estradiol (10(-8) M) modified the inhibition of PRL release induced by bromocriptine with a half-inhibitory concentration displaced from 3 X 10(-11) M (control) to 3 X 10(-10) M (estradiol). These data demonstrate that the absence of TRH effect observed in some human prolactinomas is not linked to the absence of TRH receptor in such tumor cells. TRH responsiveness is always restored in the presence of dopamine (DA) at appropriate concentration. This TRH/DA interaction seems specific while not observed under T3 inhibition of PRL. Furthermore, estrogens, while presenting a variable stimulatory effect upon basal PRL, antagonize the dopaminergic inhibition of PRL release.     

Effect of fenfluramine on growth hormone and prolactin secretion in obese subjects

Obese subjects show a subnormal growth hormone (GH) and prolactin (PRL) release in response to a variety of stimuli. Fenfluramine, an anorexiant drug used in obesity therapy, may have some effects on hypothalamic-pituitary function mediated by serotoninergic stimulation. The present investigation in obese subjects was carried out to study the effects of fenfluramine (60 mg orally) on GH and PRL secretion after intravenous arginine infusion. Ten volunteer obese females were studied and compared with 10 volunteer normal weight controls. In the obese group the GH response to arginine was significantly lower than in control group. Fenfluramine administration restored the subnormal GH response to arginine in obese subjects. The PRL response to arginine in obese women was subnormal. Fenfluramine administration restored the response of PRL to arginine infusion to normal. In conclusion, fenfluramine--under acute circumstances--enhances the hypothalamic-pituitary response to arginine in obese subjects. The decreased GH and PRL output in obese subjects is not due to an absolute hormonal deficiency and this effect of fenfluramine on GH secretion may--due to its lipolysis stimulation--be useful in obesity treatment.     

Disturbed prolactin responses to dopamine-related substances in patients with acromegaly and hyperprolactinemia

We undertook this study, because conflicting data were reported about the dopaminergic regulation of prolactin (PRL) secretion in patients with acromegaly and hyperprolactinemia. In order to clarify the dopaminergic regulation of PRL secretion in patients with acromegaly and hyperprolactinemia, the effects of nomifensine, a central dopamine agonist, FK 33-824, a centrally antidopaminergically acting agent, and domperidone, a peripheral dopamine antagonist, on plasma PRL in these patients were studied. The results were compared with those observed in normal subjects and hyperprolactinemic patients, with or without a pituitary tumor. Nomifensine did not lower the PRL levels and FK 33-824 did not raise the PRL levels in acromegalic patients. In hyperprolactinemic patients, nomifensine did not lower the PRL levels and FK 33-824 failed to raise the PRL levels. Domperidone did not increase PRL in about a third of acromegalic patients, while TRH increased PRL in the all normoprolactinemic acromegalic patients. These results suggest that in acromegalic patients there may be a disturbance in dopamine related neurotransmission and that such disorders also seem to be present in patients with hyperprolactinemia, with or without a pituitary tumor.     

Interaction between opiates and hypothalamic dopamine on prolactin release.

Opiate stimulation of prolactin (PRL) release appears to involve a hypothalamic mechanism(s). The present study utilized both central acting drugs and direct measurement of hypothalamic dopamine (DA) to investigate this problem. Administration of L-dopa, the precursor of DA; piribedil, a DA agonist; or amineptine, a DA reuptake inhibitor, each decreased serum PRL concentrations. Morphine sulfate (MS) and haloperidol (HAL) significantly increased serum PRL levels. L-dopa and piribedil reversed the stimulatory effect of MS on serum PRL concentrations by increasing dopamine activity. MS blocked the inhibitory effects of amineptine on serum PRL release, possibly by decreasing the concentration of DA available for reuptake. Injection of subeffective doses of HAL concurrently with a subeffective dose of MS increased serum PRL concentrations, by an additive inhibitory action on dopaminergic activity. β-endorphin, an endogenous opioid peptide, decreased the rate of DA turnover in the median eminence, and increased serum PRL levels approximately 10 - fold. These observations indicate that opiates stimulate PRL release by decreasing DA activity in the median eminence.     

Involvement of hypothalamic vasoactive intestinal polypeptide (VIP) in prolactin secretion induced by serotonin in rats

To study the possible involvement of hypothalamic vasoactive intestinal polypeptide (VIP) in regulating the secretion of prolactin (PRL), the effect of anti-VIP rabbit serum on serotonin (5-HT)-induced PRL release was examined in urethane-anesthetized male rats. Anti-VIP serum (AVS) or normal rabbit serum (NRS) was infused into a single hypophysial portal vessel of the rat for 40 min at a rate of 2 microliters/min with the aid of a fine glass cannula and 5-HT was injected into a lateral ventricle 10 min after the start of the infusion. Intraventricular injection of 5-HT (10 micrograms/rat) caused an increase in plasma PRL levels in control animals infused with NRS and 5-HT-induced PRL release was blunted in animals infused with AVS (mean +/- SE peak plasma PRL: 118.9 +/- 19.8 ng/ml vs 54.7 +/- 16.2 ng/ml, p less than 0.05). These findings suggest that the secretion of PRL induced by 5-HT is mediated, at least in part, by hypothalamic VIP release into the hypophysial portal blood in the rat.