Prolactin Release In Response Research Articles

Partial loss of arcuate kisspeptin neurons in female rats stimulates luteinizing hormone and decreases prolactin secretion induced by estradiol.

Kisspeptin, neurokinin, and dynorphin (KNDy) neurons in the arcuate nucleus (ARC) control luteinizing hormone (LH) and prolactin (PRL) release, although their role in conveying the effects of estradiol (E2 ) to these hormones is not well understood. We performed a longitudinal evaluation of female rats in which KNDy neurons were ablated using a neurokinin-3 receptor agonist conjugated with saporin (NK3-SAP) to investigate the impact of the reduction of KNDy neurons on the E2 regulation of gonadal and PRL axes. NK3-SAP rats, bearing a moderate loss of ARC kisspeptin-immunoreactive (-IR) neurons (50%-90%), displayed irregular estrous cycles but essentially unaltered follicular development and a normal number of corpora lutea. Rats were then ovariectomized (OVX) and treated with a positive-feedback dose of E2 (OVX + E2 ). LH and PRL were measured in the tail blood by an enzyme-linked immunosorbent assay. The E2 -induced LH surge was amplified, whereas the PRL rise was decreased in NK3-SAP rats compared to Blank-SAP control. After 10 days of no hormonal treatment, basal LH levels were equally elevated in NK3-SAP and controls. Tyrosine hydroxylase (TH) phosphorylation in the median eminence, in turn, was increased in NK3-SAP rats, with no change in the number of ARC TH-IR neurons. Thus, KNDy neurons exert concurrent and opposite roles in the E2 -induced surges of LH and PRL. The partial loss of KNDy neurons disrupts ovarian cyclicity but does not preclude ovulation, consistent with the disinhibition of the LH preovulatory surge. Conversely, KNDy neurons tonically inhibit the enzymatic activity of tuberoinfundibular dopaminergic neurons, which appears to facilitate PRL release in response to E2 .

Maternal plasma levels of oxytocin during breastfeeding-A systematic review.

IntroductionOxytocin is a key hormone in breastfeeding. No recent review on plasma levels of oxytocin in response to breastfeeding is available.Materials and methodsSystematic literature searches on breastfeeding induced oxytocin levels were conducted 2017 and 2019 in PubMed, Scopus, CINAHL, and PsycINFO. Data on oxytocin linked effects and effects of medical interventions were included if available.ResultsWe found 29 articles that met the inclusion criteria. All studies had an exploratory design and included 601 women. Data were extracted from the articles and summarised in tables. Breastfeeding induced an immediate and short lasting (20 minutes) release of oxytocin. The release was pulsatile early postpartum (5 pulses/10 minutes) and coalesced into a more protracted rise as lactation proceeded. Oxytocin levels were higher in multiparous versus primiparous women. The number of oxytocin pulses during early breastfeeding was associated with greater milk yield and longer duration of lactation and was reduced by stress. Breastfeeding-induced oxytocin release was associated with elevated prolactin levels; lowered ACTH and cortisol (stress hormones) and somatostatin (a gastrointestinal hormone) levels; enhanced sociability; and reduced anxiety, suggesting that oxytocin induces physiological and psychological adaptations in the mother. Mechanical breast pumping, but not bottle-feeding was associated with oxytocin and prolactin release and decreased stress levels. Emergency caesarean section reduced oxytocin and prolactin release in response to breastfeeding and also maternal mental adaptations. Epidural analgesia reduced prolactin and mental adaptation, whereas infusions of synthetic oxytocin increased prolactin and mental adaptation. Oxytocin infusion also restored negative effects induced by caesarean section and epidural analgesia.ConclusionsOxytocin is released in response to breastfeeding to cause milk ejection, and to induce physiological changes to promote milk production and psychological adaptations to facilitate motherhood. Stress and medical interventions during birth may influence these effects and thereby adversely affect the initiation of breastfeeding.

Influence of the estrous cycle on prolactin secretion induced by acute stress in nulliparous and primiparous rats

Prolactin is classically considered a hormone related to the development of the mammary glands during pregnancy and the production of milk in the postpartum. The release of this pituitary hormone can be interfered by stress, resulting in increased production. Physiological factors such as reproductive experience, sum of pregnancy, childbirth and lactation, and the phase of the estrous cycle has also an action on the secretion of prolactin, reducing their serum concentration. In previous studies, we observed that reproductive experience is able to modulate the release of prolactin in response to acute stress and that this is related to the type of stress applied in rats. In this context, the aim of this work was to study the influence of the estrous cycle on prolactin serum concentrations during the first hour of induction of acute stress in nulliparous and primiparous rats. The results indicated that reproductive experience modulates the secretion of prolactin released in response to acute stress and that this is dependent on the stage of the estrous cycle

Stretch-activated cation channel TRPV4 mediates hyposmotically induced prolactin release from prolactin cells of mozambique tilapia Oreochromis mossambicus

In teleost fish, prolactin (PRL) is an important hormone for hyperosmoregulation. The release of PRL from the pituitary of Mozambique tilapia is stimulated by a decrease in extracellular osmolality. Previous studies have shown that hyposmotically induced PRL release is linked with cell volume changes, and that stretch-activated Ca(2+) channels are likely responsible for the initiation of the signal transduction for PRL release. In this study, we identified the stretch-activated Ca(2+) channel transient receptor potential vanilloid 4 (TRPV4) from the rostral pars distalis (RPD) of tilapia acclimated to freshwater (FW). TRPV4 transcripts were ubiquitously expressed in tilapia; the level of expression in RPDs of FW-acclimated fish was lower than that found in RPDs of seawater (SW)-acclimated fish. Immunohistochemical analysis of the pituitary revealed that TRPV4 is localized in the cell membrane of PRL cells of both FW and SW tilapia. A functional assay with CHO-K1 cells showed that tilapia TRPV4 responded to a decrease in extracellular osmolality, and that its function was suppressed by ruthenium red (RR) and activated by 4α-phorbol 12,13-didecanoate (4aPDD). Exposure of dissociated PRL cells from FW-acclimated tilapia to RR blocked hyposmolality induced PRL release. PRL release, on the other hand, was stimulated by 4aPDD. These results indicate that PRL release in response to physiologically relevant changes in extracellular osmolality is mediated by the osmotically sensitive TRPV4 cation channel.

Evidence of an enhanced central 5HT response in irritable bowel syndrome and in the rat maternal separation model

Efforts to define either a biomarker for irritable bowel syndrome (IBS) or a valid animal model have proven disappointing. The aims of this study were to determine if buspirone stimulates prolactin release through the 5-hydroxytryptamine (5HT)1a receptor and whether this response is altered in patients with IBS and in the rat maternal separation model. Buspirone (30 mg) was used to stimulate prolactin release in 40 patients with IBS and in 40 healthy controls. In study 1, 10 IBS patients and 10 controls underwent pretreatment with pindolol (5HT1a antagonist) or placebo followed by buspirone. In study 2, 30 patients with IBS and 30 healthy controls had prolactin release stimulated by buspirone. Maternally separated and nonseparated rats were also treated with buspirone and prolactin monitored. Serotonin metabolites were measured together with the expression of the 5HT1a and serotonin transporter (SERT) gene. Pindolol produced a dose-dependent decrease in the buspirone prolactin response. Patients with IBS and maternally separated rats showed an exaggerated release of prolactin in response to buspirone. In the animal model, an increased turnover of 5HT was found in the brainstem together with a trend toward increased activity of the SERT gene. In conclusion altered central serotonin responses are found in both IBS and in an animal model.

The effects of head cooling on endurance and neuroendocrine responses to exercise in warm conditions

The present study investigated the effects of head cooling during endurance cycling on performance and the serotonergic neuroendocrine response to exercise in the heat. Subjects exercised at 75 % VO2max to volitional fatigue on a cycle ergometer at an ambient temperature of 29±1.0 °C, with a relative humidity of approximately 50 %. Head cooling resulted in a 51 % (p<0.01) improvement in exercise time to fatigue and Borg Scale ratings of perceived exertion were significantly lower throughout the exercise period with cooling (p<0.01). There were no indications of peripheral mechanisms of fatigue either with, or without, head cooling, indicating the importance of central mechanisms. Exercise in the heat caused the release of prolactin in response to the rise in rectal temperature. Head cooling largely abolished the prolactin response while having no effect on rectal temperature. Tympanic temperature and sinus skin temperature were reduced by head cooling and remained low throughout the exercise. It is suggested that there is a coordinated response to exercise involving thermoregulation, neuroendocrine secretion and behavioural adaptations that may originate in the hypothalamus or associated areas of the brain. Our results are consistent with the effects of head cooling being mediated by both direct cooling of the brain and modified cerebral artery blood flow, but an action of peripheral thermoreceptors cannot be excluded.

The effects of head cooling on endurance and neuroendocrine responses to exercise in warm conditions.

The present study investigated the effects of head cooling during endurance cycling on performance and the serotonergic neuroendocrine response to exercise in the heat. Subjects exercised at 75 % VO(2max) to volitional fatigue on a cycle ergometer at an ambient temperature of 29+/-1.0 degrees C, with a relative humidity of approximately 50 %. Head cooling resulted in a 51 % (p<0.01) improvement in exercise time to fatigue and Borg Scale ratings of perceived exertion were significantly lower throughout the exercise period with cooling (p<0.01). There were no indications of peripheral mechanisms of fatigue either with, or without, head cooling, indicating the importance of central mechanisms. Exercise in the heat caused the release of prolactin in response to the rise in rectal temperature. Head cooling largely abolished the prolactin response while having no effect on rectal temperature. Tympanic temperature and sinus skin temperature were reduced by head cooling and remained low throughout the exercise. It is suggested that there is a co-ordinated response to exercise involving thermoregulation, neuroendocrine secretion and behavioural adaptations that may originate in the hypothalamus or associated areas of the brain. Our results are consistent with the effects of head cooling being mediated by both direct cooling of the brain and modified cerebral artery blood flow, but an action of peripheral thermoreceptors cannot be excluded.

FISH OSMOREGULATE WITH OUABAIN

Ouabain, a potent inhibitor of the enzyme Na+/K+-ATPase, is known to be a steroid hormone in mammals that is involved in blood pressure and volume regulation. Recently, a group from the University of Hawaii examined whether ouabain also acts as a hormone in fish and reported that ouabain is present in the plasma and various tissues of the euryhaline Mozambique tilapia, Oreochromis mossambicus. When the researchers transferred tilapia between fresh and salty water, they discovered that changes in plasma concentrations of ouabain in tilapia were well correlated with changes in plasma osmolality and cortisol, an important hormone during salinity change. Now, this same research group has followed up with an equally intriguing analysis of the functional role of ouabain in fish osmoregulation.The present study set out to establish whether ouabain interacts with growth hormone and prolactin (known osmoregulatory hormones in fish) in the same manner as cortisol. During seawater acclimation, cortisol stimulates Na+/K+-ATPase activity and the proliferation of chloride cells that are responsible for the active extrusion of Cl-. In addition, cortisol stimulates the release of growth hormone, which is also involved in seawater adaptation, and inhibits the release of prolactin, an important hormone in freshwater osmoregulation, from the pituitary gland. Prolactin release is dependent on calcium entering pituitary gland cells and the synthesis of cAMP, both of which are prevented by cortisol.To assess the role of ouabain in fish osmoregulation, Kajimura, Grau and the group examined the release of osmoregulatory hormones by tilapia pituitary glands. They isolated whole pituitary glands from tilapia and placed them individually in a 96-well plate containing 200 μl of incubation media. With this in vitro preparation, they measured prolactin and growth hormone release from tilapia pituitary glands in response to different doses of ouabain. To see if ouabain, like cortisol, inhibits prolactin release by preventing calcium uptake and cAMP synthesis, they measured prolactin release in response to calcium (using the calcium ionophore A23187) and to cAMP (using the analogue dbcAMP and the phosphodiesterase inhibitor IBMX) in the presence or absence of ouabain. The group found that at physiological concentrations,ouabain exerted a dose-dependent inhibitory effect on prolactin, whereas supra-physiological doses of ouabain stimulated prolactin release. By contrast, ouabain stimulated growth hormone release at lower concentrations but had an inhibitory effect at higher levels. Both A23187 and dbcAMP + IBMX had stimulatory effects on prolactin release, and these effects were inhibited by ouabain when it was also placed in the incubation media. This suggests that, like cortisol, ouabain regulates the mechanism of prolactin release. Furthermore, using microspectrofluorometry and a calcium-sensitive dye, the team was able to quantify `real-time' changes in calcium levels within pituitary cells. Their data indicated that at physiological concentrations,ouabain rapidly reduces intracellular calcium concentrations, just as cortisol does.The group has shown convincingly that, similar to the actions of cortisol during salinity change, ouabain plays an important role in fish osmoregulation by inhibiting the release of prolactin via the Ca2+ and cAMP signal transduction pathways. The team believes that ouabain in the hypothalamus of the brain may be involved in the regulation of pituitary prolactin release and hope to prove this hypothesis in the future by using a ouabain-specific antibody and immunocytochemistry. Until then, we will wait for more news about this exciting new fish hormone!

Sensitivity to Stress-Induced Reproductive Dysfunction Linked to Activity of the Serotonin System

Many forms of stress, including psychosocial stress, may be associated with reproductive dysfunction. Women seeking treatment for infertility often have been subjected to multiple stressors. The authors have developed an experimental primate model of hypothalamic amenorrhea. Combining mild psychosocial stress with a mild diet and moderate exercise suppresses reproductive function in this model. Because serotonergic activity is decreased in persons who are inordinately sensitive to stress, a study was planned to determine whether differences in endogenous function of the central serotonergic system can be found in stress-sensitive and stress-resistant female cynomolgus macaques. Sedated monkeys previously categorized as highly stress-resistant (HSR, normal menstrual cyclicity through 2 stress cycles), medium stress-resistant (MSR, ovulatory in only the first cycle), or stress-sensitive (SS, anovulatory when first exposed to stress) were challenged with an intravenous dose of 5 mg/kg of the serotonin-releasing drug fenfluramine. The hypothesis was that SS animals would have lower levels of central serotonergic activity. Thyrotropin-releasing hormone (TRH) was administered to control for differences in pituitary stores of prolactin or corticotropin-releasing factor (CRF) to control for low levels of ACTH. Release of prolactin in response to fenfluramine was significantly greater in the HSR animals than in the MSR and SS groups. Cortisol responses to fenfluramine were higher in the SS group than in either group of stress-resistant animals. Similar responses to fenfluramine were no longer evident after stimulation with TRH combined with CRF. These studies in macaques indicate differing reproductive hormone responses to moderate stress. Stress sensitivity correlates with prolactin secretion in response to fenfluramine, which promotes the release of serotonin. Highly stress-resistant animals have higher endogenous serotonin levels than do stress-sensitive animals in the absence of stress. Whether this reflects secretion of ovarian steroids, social status, or genetic predisposition remains to be determined.

PROLACTIN SECRETION IN HYPOTHYROID ENDOTOXEMIC RATS: INVOLVEMENT OF L-ARGININE AND NITRIC OXIDE SYNTHASE

The identification of nitric oxide (NO) within the hypothalamus and pituitary gland has suggested its role as modulator of the activity on hypothalamic-pituitary axis. Hypothalamic NO synthase (NOS) is known to be regulated by thyroid hormones. We investigated the effects of previous injection of N-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, and L-arginine (L-Arg), the substrate for NO synthesis, on prolactin (PRL) secretion, through the lipopolysaccharide (LPS)-induced inflammatory response in thyroidectomized (TX) rats. TX or sham-operated (N) rats were intraperitoneally (i.p.) injected with L-NAME (10 mg kg) or L-Arg (200 mg kg) or the same volume of vehicle (saline solution) 30 min before endotoxemia-induction with LPS at 250 mug (100 g body weight), i.p.. In N rats, NO increased PRL release in response to endotoxemia, whereas in hypothyroid rats, NO appeared to have the opposite effect. Our data support the hypothesis that NO exerts a modulatory influence on PRL secretion after LPS-induced inflammatory response.

Sensitivity to stress-induced reproductive dysfunction linked to activity of the serotonin system

To use a nonhuman primate model and determine whether individuals sensitive to stress-induced reproductive dysfunction have lower activity of central serotonergic neurons under nonstressed conditions. The activity of the central serotonergic system was assessed by measuring responsiveness to a fenfluramine challenge (5 mg/kg, IV) in sedated monkeys previously categorized as highly stress resistant (HSR; n = 4; normal menstrual cyclicity through two stress cycles), medium stress resistant (MSR; n = 5; ovulatory in the first stress cycle but anovulatory in the second stress cycle), or low stress resistant (i.e., stress sensitive, SS; n = 4; anovulatory as soon as stress is initiated). To control for differences in pituitary stores of prolactin or ACTH, the animals were subsequently administered a bolus of thyrotropin-releasing hormone (3 microg/kg) plus corticotropin releasing factor (CRF), (3 microg/kg). Oregon National Primate Research Center, Animal Services Building. Female cynomolgus macaques exhibiting normal menstrual cycles. Administration of fenfluramine, a serotonin-releasing drug. Serum concentrations of prolactin (PRL) and cortisol (F). Prolactin release in response to fenfluramine was significantly greater in the HSR group compared with the MSR or SS groups. In contrast, cortisol was higher in the SS group compared with the other two groups. Similar responses were not evident after thyrotropin-releasing hormone + CRF stimulation. The lower PRL response to fenfluramine in the stress-sensitive animals suggests that stress-sensitive individuals have decreased activity in central serotonergic neurons. However, the F data suggest that the hypothalamic-pituitary-adrenal axis in stress-sensitive individuals is highly responsive to even small increases in serotonin.

The effect of morphine and naloxone on the release of prolactin during machine milking in dairy cows.

The aim of the study was to determine the role of opioids modulating the release of prolactin (PRL) in response to milking in sixteen Brown-Swiss dairy cows. Two experiments were carried out to measure the dose-related effect of morphine and the effect of the opioid antagonist naloxone (NAL), with or without morphine. In the first experiment, six cows were injected (via catheter) on 3 consecutive days after the control milking (0 mg) with 21, 70 and 210 mg morphine-HCl 10 min before the start of the morning milking. The second experiment was divided into two parts. In the first part, four cows were injected after control morning milking with 210 mg morphine, 10 min before the start of the following morning milking. This was followed on the next day by an application of 210 mg NAL (15 min before the start of milking) and 210 mg morphine. In the second part, after control milking for 1 d, six cows were injected with 210 mg NAL 10 min before milking. Morphine at the highest dose tended to stimulate basal PRL levels in the first and second experiments (P < 0.10). PRL increased in response to machine milking but morphine did not stimulate its release further. NAL alone, or when given with morphine did not influence the release of PRL in response to machine milking. However, NAL was effective in suppressing the increase in basal levels of PRL caused by morphine. In conclusion, although morphine tended to stimulate basal levels of PRL before milking, the release of PRL during milking seemed not to be regulated by opioids.

A preliminary study of buspirone stimulated prolactin release in generalised social phobia: evidence for enhanced serotonergic responsivity?

Serotonergic dysfunction has been postulated to play a role in the aetiology of social phobia. Buspirone, which is a partial agonist at 5HT1A receptors, increases prolactin release and may be used as a probe to examine serotonergic responses, dysfunction of which may be relevant to the pathophysiology of social phobia. We compared buspirone stimulated prolactin release in 14 patients with generalised social phobia and 14 healthy controls. Buspirone 30 mg was administered orally and prolactin release over 180 min was monitored. Overall, patients with generalised social phobia had greater prolactin release in response to buspirone challenge than healthy comparison subjects. There was no correlation between prolactin response and measures of severity of social phobia. Patients with generalised social phobia had enhanced central serotonergic responses, an abnormality shared with some other anxiety disorders and which may be of aetiological significance.

Isolation and Characterization of a Homologue of Mammalian Prolactin-Releasing Peptide from the Tilapia Brain and Its Effect on Prolactin Release from the Tilapia Pituitary

In the tilapia (Oreochromis mossambicus), as in many teleosts, prolactin (PRL) plays a major role in osmoregulation in freshwater. Recently, PRL-releasing peptides (PrRPs) have been characterized in mammals. Independently, a novel C-terminal RF (arginine-phenylalanine) amide peptide (Carrasius RF amide; C-RFa), which is structurally related to mammalian PrRPs, has been isolated from the brain of the Japanese crucian carp. The putative PrRP was purified from an acid extract of tilapia brain by affinity chromatography with antibody against synthetic C-RFa and HPLC on a reverse-phase ODS-120 column. The tilapia PrRP cDNA was subsequently cloned by polymerase chain reaction. The cDNA consists of 619 bp encoding a preprohormone of 117 amino acids. Sequence comparison of the isolated peptide and the preprohormone revealed that tilapia PrRP contains 20 amino acids and is identical to C-RFa. Incubation of the tilapia pituitary with synthetic C-RFa (100 nM) significantly stimulated the release of two forms of tilapia PRL (PRL188 and PRL177). However, the effect of C-RFa was less pronounced than the marked increase in PRL release in response to hyposmotic medium. The ability of C-RFa to stimulate PRL release appears to be specific, since C-RFa failed to stimulate growth hormone release from the pituitary in organ culture. In contrast, rat and human PrRPs had no effect on PRL release. C-RFa was equipotent with chicken GnRH in stimulating PRL release in the pituitary preincubated with estradiol 17β. Circulating levels of PRL were significantly increased 1 h after intraperitoneal injection of 0.1 μg/g of C-RFa in female tilapia in freshwater but not in males. These results suggest that C-RFa is physiologically involved in the control of PRL secretion in tilapia.

Desensitization of angiotensin II: effect on [Ca2+]i, inositol triphosphate, and prolactin in pituitary cells.

Activation of pituitary angiotensin (ANG II) type 1 receptors (AT1) mobilizes intracellular Ca2+, resulting in increased prolactin secretion. We first assessed desensitization of AT1 receptors by testing ANG II-induced intracellular Ca2+ concentration ([Ca2+](i)) response in rat anterior pituitary cells. A period as short as 1 min with 10(-7) M ANG II was effective in producing desensitization (remaining response was 66.8 +/- 2.1% of nondesensitized cells). Desensitization was a concentration-related event (EC(50): 1.1 nM). Although partial recovery was obtained 15 min after removal of ANG II, full response could not be achieved even after 4 h (77.6 +/- 2.4%). Experiments with 5 x 10(-7) M ionomycin indicated that intracellular Ca2+ stores of desensitized cells had already recovered when desensitization was still significant. The thyrotropin-releasing hormone (TRH)-induced intracellular Ca2+ peak was attenuated in the ANG II-pretreated group. ANG II pretreatment also desensitized ANG II- and TRH-induced inositol phosphate generation (72.8 +/- 3.5 and 69.6 +/- 6.1%, respectively, for inositol triphosphate) and prolactin secretion (53.4 +/- 2.3 and 65.1 +/- 7.2%), effects independent of PKC activation. We conclude that, in pituitary cells, inositol triphosphate formation, [Ca2+](i) mobilization, and prolactin release in response to ANG II undergo rapid, long-lasting, homologous and heterologous desensitization.

Endocrine mechanism of action of toremifene at the level of the central nervous system in advanced breast cancer patients

To differentiate the antagonistic and agonistic effect of toremifene at the level of the hypothalamus-hypophysis axis a leutinizing hormone-releasing hormone (LHRH) test was performed during a phase II clinical trial. In 15 postmenopausal patients with advanced breast cancer, follicle-stimulating hormone (FSH) and LH release--induced by an LHRH agonist (Suprefact injection, 0.5 mg s.c.)--was monitored during a 16-week period of toremifene treatment (60 mg/day p.o.). Prolactin, estradiol, and sex hormone-binding globulin (SHBG) levels were also measured. The functional test was carried out prior to toremifene therapy and then 4, 8, 12, and 16 weeks afterward. The drug sensitized the pituitary to the action of the gonadotrophins; the LHRH-induced FSH and LH release showed a considerably increasing tendency during the toremifene therapy. Estradiol levels decreased statistically significantly and SHBG levels showed a statistically significant increase. A decreased level of prolactin is the sign of an antiestrogenic effect of toremifene on the hypophysis and, as a result, provides evidence for a direct influence of toremifene upon the pituitary. An increase in LH and prolactin release in response to the LHRH test was characteristic in the responders. According to the LHRH test, the antagonistic effect of toremifene seems to be more dominant than the concomitantly existing agonistic property. Neither clinical nor endocrinological side effects could be observed at the level of the CNS during a prolonged period of toremifene administration.

Alpha-MSH potentiates the responsiveness of mammotropes by increasing Ca2+ entry.

It is well known that the suckling stimulus renders mammotropes considerably more responsive to prolactin (PRL)-releasing stimuli, and the neurointermediate lobe peptide alpha-melanocyte-stimulating hormone (alpha-MSH) has been proposed to play a pivotal role in this priming. The objectives of the present study were to determine whether alpha-MSH could act directly on pituitary cells to potentiate PRL release in response to two physiologically relevant PRL secretagogues, thyrotropin-releasing hormone (TRH) and ATP, and, if so, to identify the mechanism by which this priming phenomenon is manifested. To this end, we cultured anterior pituitary cells from lactating rats overnight and then subjected them to a reverse hemolytic plaque assay for PRL to evaluate their responses to various test agents. We found that alpha-MSH, which had no effect on PRL export when tested alone, augmented by more than threefold the secretory responses to TRH and ATP. Next, we utilized digital-imaging fluorescence microscopy of fura 2 to evaluate the role of intracellular Ca2+ in this process. We found that PRL export induced by pharmacological activation of L-type voltage-operated calcium channels was also potentiated by alpha-MSH, as was Ca2+ entry induced by TRH. Our results indicate that alpha-MSH acts as a mammotrope-priming agent on a subset of mammotropes by increasing Ca2+ entry induced by PRL secretagogues.

Attenuation of the magnitude of suckling-induced prolactin release with advancing lactation: Mechanisms

To study why suckling-induced plasma prolactin levels decline in magnitude with advancing lactation, we examined prolactin release in lactating rats following suckling and pharmacologic manipulations during early, mid- and late lactation. On day 2 of lactation, litters were adjusted to 8 pups. On day 3, dams were implanted with an atrial catheter and experiments were conducted on lactation days 5, 11 and 17. To examine suckling-induced prolactin release, pups were removed at 0800 h, an extension was attached to the catheter at 1100 h, and pups returned to dams at 1200 h. Blood samples were obtained before, and at 10, 30, 60, 90 and 120 min after suckling started. Prolactin responses to sulpiride and thyrotropin releasing hormone (TRH) administration were studied in lactating rats separated from their litters for 4 hours. Blood samples were obtained before, and at 10, 30, 60 and 90 min after sulpiride (10 or 40 μg/kg BW) and 5, 10, 20 and 30 min after TRH (1 or 4 μg/kg BW) in rats pretreated with sulpiride. Prolactin release in response to suckling, administration of sulpiride or sulpiride and TRH diminished as lactation advanced. From these results, we conclude that refractoriness in anterior pituitary lactrotropes to prolactin-releasing stimuli is at least partially responsible for the decline in suckling-induced prolactin release with advancing lactation.

Lipopolysaccharides Inhibit Prolactin and Renin Release from Human Decidual Cells1

Human decidual tissue consists of a heterogeneous population of cells, including stromal cells, lymphocytes, and macrophages. Lipopolysaccharides (LPS), which bind to specific cell surface receptors on macrophages, have been shown to increase prostaglandin production by the decidua and amnion. To determine whether LPS may also affect decidual hormone production, we have examined the effects of LPS on the synthesis and release of prolactin and renin. Dispersed cells from term decidual tissue exposed to LPS L2880 (Escherichia coli, 1 microgram/ml) released significantly less prolactin and renin than control cells after 24 h of exposure. Maximal inhibition of prolactin (31.6%) and renin (62.5%) release was noted at 72 and 96 h of exposure, respectively (p < or = 0.0002 in each instance). The inhibition of prolactin and renin release was dose-dependent, with half-maximal inhibition at a dose of approximately 10 ng/ml. LPS caused a decrease in prolactin synthesis as well as release. In addition, LPS inhibited the stimulation of prolactin release in response to insulin, a known secretagogue of prolactin release. After 24, 48, and 72 h of exposure, the magnitude of the stimulation of prolactin release by cells exposed to insulin (100 ng/ml) in the presence of LPS (1 microgram/ml) was 84.5, 57.5, and 35.2% less, respectively, than that of cells exposed to insulin alone (p = 0.0001 in each instance). LPS L6011 (Salmonella endotoxin) also inhibited prolactin and renin release. LPS had no effect on overall protein or DNA synthesis and did not cause release of alkaline phosphatase and lactate dehydrogenase.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of ovarian surgery on the dopaminergic and opioidergic control of gonadotropin and prolactin secretion in women with polycystic ovarian disease.

Ovarian surgery has been demonstrated as an effective means to establish regular menstrual cycles and resumption of ovulation in patients with polycystic ovarian disease (PCO). We questioned whether such reinstitution of menstrual cyclicity may be associated with changes in the opioidergic and dopaminergic activity known to be aberrant in these women. Opioidergic and dopaminergic tone was therefore assessed in patients with PCO before and after ovarian laser vaporization (n = 4) or classical ovarian wedge resection (n = 4). Blood samples for the determination of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin were frequently obtained following opioidergic and/or dopaminergic antagonism affected by naloxone (4 mg i.v.) or metoclopramide (10 mg i.v.). In response to either surgical approach, circulating LH levels decreased (p < 0.01), while FSH concentrations remained unaltered. Further, LH and FSH concentrations did not noticeably change following challenges with naloxone or metoclopramide: this applied to conditions before and after ovarian surgery. Prolactin release in response to metoclopramide was markedly (p < 0.01) higher following ovarian surgery than before. Thus, both ovarian laser surgery and classical wedge resection can effectively restore normal menstrual cyclicity in PCO patients, although they failed to alter opioidergic and dopaminergic activity. Dopaminergic inhibition of prolactin secretion was further enhanced after ovarian surgery. These observations suggest that different modes of ovarian surgery are effective in influencing central gonadal control, but that the central opioidergic and dopaminergic control of gonadotropin and prolactin secretion remains unaffected by ovarian surgery in PCO women, even when menstrual cyclicity is resumed.