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PubMed1992

Altered prolactin response of the lymphocytes of tumor-bearing mice.

Interaction of prolactin and glucocorticoid on thymocytes and splenocytes of normal and tumor-bearing mice with reference to their mitogen-responsive blastogenesis has been studied. Prolactin alone had little or no mitogenic effect on thymocytes and splenocytes of normal mice but it was co-stimulatory, with ConA, in inducing blastogenesis in normal splenocytes. Thymocytes and splenocytes of tumor-bearing mice responded differently to prolactin. Hormone alone inhibited growth of thymocytes but at certain concentrations stimulated splenocytes. When cultured with prolactin and ConA, the thymocytes of tumor hosts responded with increased proliferation compared to that induced by ConA alone. Glucocorticoid suppressed ConA-induced lymphocyte proliferation in both normal and tumor-bearing mice. Prolactin reversed the inhibitory effect of glucocorticoid in normal mice but failed to abrogate inhibition in tumor hosts. Altered responsiveness of lymphocytes of tumor hosts to prolactin was not a function of circulating prolactin, as the serum prolactin level was similar in normal and tumor-bearing mice. Prolactin, however, could not reverse estradiol-induced suppression of lymphocyte proliferation. The lactogenic hormone, but not somatogenic hormones, altered the glucocorticoid inhibition of lymphocyte growth.

Animals↗

PubMed1984

Ca2+ and hormones interact synergistically to stimulate rapidly both prolactin production and overall protein synthesis in pituitary tumor cells.

Effects of Ca2+ and hormones on short-term protein synthesis were examined utilizing intact Ca2+-depleted and Ca2+-restored GH3 pituitary tumor cells as a model system. Amino acid incorporation by cells in complete growth medium during short incubations was markedly reduced by EGTA concentrations in excess of Ca2+. Thyrotropin-releasing hormone (TRH) rapidly enhanced amino acid incorporation and prolactin production, with both effects being reserved by EGTA in excess of extracellular Ca2+ or prevented by cellular Ca2+ depletion. Epidermal growth factor and phorbol myristate acetate (PMA) also stimulated amino acid incorporation and prolactin production; absolute increases in protein synthesis provided by these agents were significantly greater in Ca2+-restored than in Ca2+-depleted preparations. TRH and PMA concentrations which raised prolactin production were identical to those increasing the rate of amino acid incorporation into overall protein. The extracellular Ca2+ concentration dependencies of amino acid incorporation and prolactin production were similar and were unchanged by hormone. PMA, the most efficacious of the agents tested, and Ca2+ promoted incorporation of amino acid into the same spectrum of proteins. Stimulation of protein synthesis by hormones was not attributable to alterations in amino acid uptake, attachment to substrata, hormone binding, protein catabolism or transcription. Trifluoperazine selectively prevented the stimulation by Ca2+ of amino acid incorporation and prolactin production. Unlike total prolactin, the total protein content of GH3 cells during these short incubations was not altered by Ca2+, hormones or trifluoperazine. It is proposed that hormones and Ca2+, which have been demonstrated to regulate prolactin secretion and prolactin mRNA transcription in GH3 cells, also exert translational controls which serve to facilitate the overall expression of the prolactin gene.

Amino Acids↗

PubMed1999

Changes in levels of immunoreactive prolactin isoforms during a reproductive cycle in turkey hens.

Changes in the ratio between immunoreactive isoforms of prolactin using Western blotting and in the total prolactin content using radioimmunoassay were measured in pituitary glands from turkey hens at different physiological stages. The type of glycosylation (N- or O-linked carbohydrates) was determined using endoglycosidase digestion (N-glycosidase F, O-glycosidase, and neuraminidase). Low levels of prolactin were observed in pituitary glands from sexually immature, out-of-lay, and molting hens. Higher levels were present during the egg-laying period and the highest levels were detected in hens which expressed incubation behavior. Two immunoreactive bands of apparent molecular weights of 24 and 27 kDa were visualized on Western blots, corresponding to the nonglycosylated and glycosylated forms of prolactin, respectively. In pituitary glands from incubating turkey hens, about 70% of the prolactin was glycosylated (27-kDa isoforms), whereas about 60% was glycosylated in immature and in hens during the first egg-laying period. In pituitaries from out-of-lay and molting hens the percentage of glycosylated prolactin was 38 and 33%, respectively. Thus, higher percentages of glycosylated isoforms (27 kDa) were associated with high levels of total prolactin and lower percentages were associated with low levels of prolactin content in the pituitary gland. Digestion of the isoforms with N-glycosidase F resulted in a single band with an apparent molecular weight of 24 kDa. Partial deglycosylation was achieved using neuraminidase, whereas digestion with O-glycosidase had no apparent effect on the isoforms. Thus it appears that the glycosylated isoforms of prolactin have N-linked carbohydrates containing sialic acid.

Animals↗

PubMed1999

Effects of vasoactive intestinal peptide on prolactin secretion in three species of passerine birds.

Previous work on domesticated species has indicated that vasoactive intestinal peptide (VIP) is an important prolactin-releasing factor in these birds, but no comparative work in passerine birds has been reported. This study showed that iv injections of VIP (50-100 microg/kg body mass) result in a dramatic, but transitory, rise in plasma prolactin in Mexican jays (Aphelocoma ultramarina). Significant increases in prolactin were also observed following VIP injection in blue jays (Cyanocitta cristata) and zebra finches (Poephilla guttata). At the dosage we used, maximum levels of prolactin attained were slightly lower (Mexican jays) or very similar (blue jay and zebra finch) to the maximum prolactin levels observed in other, breeding birds of the same species. In zebra finches that initially had low prolactin, VIP injection resulted in a greater than 10-fold increase in prolactin within 10 min, but those individuals that already had elevated prolactin showed no further increase in response to VIP. Slow-release pellets of VIP implanted subcutaneously in Mexican jays and releasing 10 or 15 microg VIP/day (two or three pellets) produced a significant increase in plasma prolactin (78 and 92% rise, respectively) compared to birds with placebo pellets or with with one pellet releasing only 5 microg/day.

Animals↗

PubMed2000

Prolactin levels during the periparturitional period in the biparental cotton-top tamarin (Saguinus oedipus): interactions with gender, androgen levels, and parenting.

Unlike biparental bird and rodent species, mating and parenting occur simultaneously in cotton-top tamarins, Saguinus oedipus, providing a unique model for examining endocrine interactions. This study was designed to determine the relationship of prolactin to testicular androgens during parenting and mating. Specifically we examined (1) the patterns of postpartum prolactin excretion in male and female tamarins with and without infant survival; (2) the relationship between androgen and prolactin levels during the periparturitional period in male tamarins; and (3) male hormonal response to the postpartum mating that occurs simultaneously with paternal care. All females showed an elevation in prolactin during the first week postpartum and when infants died, female prolactin levels decreased significantly. Infant survival during the first 15 days did not influence male levels of prolactin, cortisol, or the testicular androgens testosterone and dihydrotestosterone (DHT). Prolactin did not show an inverse relationship with any of the androgens (testosterone, DHT) studied during the postpartum period. No significant differences in hormones were found between prepartum levels and the first, second, and third 5-day blocks postpartum for all 10 males. Males who had infant-care experience showed an increase in testosterone during the first 5 days postpartum and prolactin levels correlated with the number of previous births a male had experienced. However, the most significant changes in testosterone occurred in males whose mates ovulated during the first 15 days following birth in contrast to males whose mates ovulated later than 15 days. These results indicate that unlike females, male tamarins are not showing hormonal changes in response to infants. Urinary androgens did not show an inverse relationship to prolactin in male tamarins, but were elevated concurrent with the female's fertile period.

Androgens↗

PubMed1977

Stereological and biochemical analysis of prolactin and growth hormone secreting rat pituitary cells in culture. Stereology combined with non-parametrical statistics.

The secretion of prolactin is increased by treatment of prolactin producing rat pituitary cells with the hypothalamic tripeptide thyroliberin. To investigate the underlying mechanisms we used three closely related rat pituitary tumor cell strains (GH1 2C1, GH3 and GH4C1), which synthesize and spontaneously secrete prolactin and/or growth hormone. Growth hormone and prolactin released into the culture medium over a period of 24 h were measured by radioimmunoassay. Initial rates of synthesis were measured by immunoprecipitation of intracellular growth hormone and prolactin after incubation of cell cultures with 3H-leucine. The observed increase in prolactin synthesis and release was correlated with morphological effects of thyroliberin treatment. The volume density of Golgi complexes and the volume and surface densities of rough endoplasmic reticulum were compared in untreated cells and thyroliberin treated cells. As normal distribution could not be assumed the non-parametric rank test of Wilcoxon was used whereby the densities calculated for each cell section were ranked. All three morphological parameters increased after thyroliberin treatment in cells secreting prolactin only (GH4C1), implying that the increase of prolactin secretion, at least in part, is due to increased prolactin synthesis.

Animals↗

PubMed1982

Prolactin response following intravenous and oral sulpiride in healthy human subjects in relation to sulpiride concentrations.

Sulpiride (100 mg) was administered intravenously and orally to healthy human subjects. Serum concentrations of sulpiride and prolactin were followed for 36 h. Both routes of drug administration resulted in a pronounced and sustained increase in serum prolactin concentration. The prolactin response was positively correlated to the prolactin baseline value. The concentrations of prolactin remained at an elevated plateau for 9--36 h after drug treatment despite low drug concentrations. The level of this plateau was directly related to the normal circadian secretion of prolactin. The sustained prolactin elevation may be due to high affinity and strong binding of the compound to the regulating receptors or the formation of an active sulpiride metabolite. Prolactin and sulpiride concentrations were significantly correlated during the initial phase after intravenous sulpiride. Following intravenous and oral sulpiride the area under the concentration-time curve (AUC) for prolactin was similar despite a considerable difference in the sulpiride concentration.

Administration, Oral↗

PubMed1992

Ontogenic studies of the neural control of adenohypophyseal hormones in the rat. II. Prolactin.

1. Serum prolactin levels are low during the first 20 days of life and gradually increase toward puberty, in both male and female rats. 2. There is an age-related increase in the cell population engaged in prolactin secretion, as well as an increase in the synthesis of prolactin and of the amount of prolactin secreted from individual lactotropes. 3. The gradual increase in prolactin levels in the third week of life is not related to a decrease in dopaminergic inhibition but to an increase in the efficiency of prolactin releasing factors such as estrogen, serotonin, opiates, and posterior pituitary extracts. 4. Prolactin release induced by physiological factors, such as stress, cervical stimulation, or the expression of spontaneous diurnal and nocturnal surges, requires maturational events within the hypothalamic-pituitary axis which are evident at the end of the third week of life. 5. In the female rat the steadily increasing levels of prolactin are involved in the timing of puberty eclosion acting at the ovary and at the brain. 6. In the prepubertal male rat increasing titers of prolactin may be involved in testicular and accessory organ development and may facilitate the actions of luteinizing hormone, follicle stimulating hormone, and testosterone on male sexual organs.

Age Factors↗

PubMed1990

The effects of immersion and exercise on prolactin during pregnancy.

Prolactin is an important hormone during pregnancy, affecting mother, fetus, and amniotic fluid volume. Immersion is known to affect prolactin levels significantly. To determine the effect of immersion and exercise on the prolactin response during pregnancy, we examined serum prolactin levels at 15, 25, and 35 weeks' gestation and 10 weeks post partum. Twelve women completed 20 min land rest, 20 min immersion in 30 degrees C water to the xiphoid, and 20 min exercise in the water at 60% VO2max. Resting prolactin levels were 1.91 +/- 0.32, 4.55 +/- 0.5, and 5.85 +/- 0.27 nmol.l-1 +/- standard error of the mean at 15, 25, and 35 weeks' gestation, respectively. Postpartum lactating women had a resting mean prolactin level of 3.95 +/- 1.6 versus 0.22 +/- 0.4 nmol.l-1 in non-lactating women. Prolactin levels declined significantly during immersion even after correction for dilution by plasma volume shifts. The immersion response was inversely related to the duration of pregnancy with 29%, 22%, and 12% drops during 15-, 25- and 35-week trials, respectively. Compared to rest, exercise prolactin levels remained depressed during the 15th and 25th week trials. We hypothesize that immersion in water caused prolactin levels to decline.

Adult↗

PubMed1988

Effects of prolactin on gametes and zygotes during in vitro fertilization in mice.

Hyperprolactinemia is one of the major causative factors of infertility. However, the effect of prolactin on gametes during in vitro fertilization has not been elucidated. In the present study, the effects of mouse prolactin on the motility of spermatozoa, in vitro fertilization, and in vitro development of the zygote were investigated in mice using media containing three different concentrations (10, 50, and 100 ng/ml) of mouse prolactin. The development of unfertilized and fertilized oocytes (zygotes) was not affected in vitro by prolactin regardless of the amount of prolactin added to culture media. However, the fertilizing capacity of the spermatozoa was suppressed when they were preincubated for 90 min in culture media containing prolactin at concentrations of 50 and 100 ng/ml. The motility of spermatozoa was not affected by prolactin regardless of the concentration of prolactin used for preincubation. The present study indicates that prolactin may have some effects on the capacitation process of spermatozoa in vitro. This result should be taken into consideration in in vitro fertilization and embryo transfer procedures in humans.

Animals↗

PubMed1984

Prolactin concentration in plasma and susceptibility to mammary tumors in female rats from different strains treated chronically with estradiol-17 beta.

Prolactin is associated with the development of mammary tumors in rats. The aim of the present study was to evaluate whether strain differences in susceptibility to the development of mammary tumors could be explained by genetic differences in the response of the pituitary to chronic stimulation by estrogens. Prolactin levels were measured in plasma from rats of the Sprague-Dawley, Wistar WAG/Rij and Brown Norway BN/BiRij strains before and at different times after subcutaneous implantation of estradiol-17 beta in cholesterol/paraffin pellets. In all strains plasma prolactin was elevated from the second week after implantation of the pellet, although there were quantitative differences between the responses. At 32 weeks after implantation of the pellets the plasma level of prolactin in Sprague-Dawley rats was 1247 +/- 367 ng NIAMDD prolactin RP-1/ml (mean +/- S.E.M), whereas Wistar WAG/Rij and Brown Norway BN/BiRij had plasma prolactin levels of 679 +/- 211 and 182 +/- 19 ng/ml respectively. Between 52 and 104 weeks after implantation these values rose to 4016 +/- 1116, 5004 +/- 1053 and 808 +/- 129 ng/ml respectively. The plasma concentration of prolactin of rats in this age group was strongly associated with the occurrence of pituitary adenomas in all three strains. In untreated rats, the concentration of prolactin in the plasma increased with age to only 200-400 ng/ml at 12-24 months of age but no significant differences were observed between the three rat strains. It is concluded that observed differences in spontaneous and estrogen-mediated mammary tumor development in these rat strains cannot be explained by genetic differences in the plasma concentration of prolactin.

Adenoma↗

PubMed1997

Dopamine D2 receptor mediates both inhibitory and stimulatory actions on prolactin release.

Dopamine is considered to be the major physiological tonic inhibitor of prolactin release, yet there is increasing evidence showing that it can also stimulate prolactin release from lactotrophs. In primary cultured lactotrophs, the major dopamine receptors responsible for inhibiting prolactin release are dopamine D2 receptors. A dopamine receptor subtype may be responsible for the stimulatory action, yet one cannot exclude the possibility that a dopamine D2 receptor can play dual roles. This study was therefore undertaken to investigate if dopamine both stimulates and inhibits prolactin secretion through activation of the same dopamine D2 receptor. GH4ZR7 cells, which have only one type of dopamine receptors--D2s, were perifused with different concentrations of dopamine, and the perifusate was assayed for prolactin; 10(-7) mol/L dopamine stimulated prolactin release (p < 0.05; n = 5), whereas 5 x 10(-4) mol/L dopamine inhibited prolactin secretion (p < 0.05; n = 5). In the pertussis toxin-treated cells, 10(-7) mol/L dopamine stimulated prolactin release (p < 0.05; n = 5), and 5 x 10(-4) mol/L dopamine did not significantly change the rate of prolactin release. These results indicate that both the stimulatory and inhibitory actions of dopamine are likely mediated by the same D2 receptor subtype, since GH4ZR7 cells express only D2s receptors. They also confirm that the inhibitory action of dopamine is mediated through a Gi protein; and the stimulatory action of dopamine is mediated through a PTX-insensitive pathway. These findings suggest that D2 receptors are coupled to both Gi and Gs proteins.

Animals↗

PubMed1984

Alteration by prolactin of surface charge and membrane fluidity of rat 13762 mammary ascites tumor cells.

Intraperitoneal injection of ovine prolactin (100 micrograms/d) in Fischer 344 rats bearing transplantable 13762 mammary ascites tumor (MAT) cells modifies the surface charge density and membrane fluidity of the tumor cells. In each of five experiments the mean electrophoretic mobility (epm) of MAT cells taken from prolactin-treated rats was significantly lower than that of cells from nonhormone-treated controls. Prolactin concentrations were increased in vivo by (a) direct intraperitoneal injection of ovine prolactin; (b) subcutaneous implantation of diethylstilbestrol-containing silastic capsules to produce pituitary prolactin secreting tumors; or (c) a single subcutaneous injection of polyestradiol phosphate, a long-acting estrogen. In an effort to establish that the prolactin effect was a direct one, two in vivo protocols were used: (a) MAT cells were coincubated with anterior pituitary halves obtained from nontumor-bearing littermates; or (b) rat or ovine prolactin was added to serum-free culture media containing MAT cells. In both protocols, the epm of the prolactin-treated cells was significantly lower. The isoelectric focusing pH of whole cells was increased by prolactin treatment from 4.93 to 5.12, consistent with a reduction in the number of surface carboxyl groups. The fluidity of membranes of treated cells was drastically increased, as measured by spin-label probe rotation rates. These combined results imply that the hormone exerts its effect by stimulating events in the cell that lead to a reduction of the average density of carboxylic acid residues on the tumor cell surface.

Animals↗

PubMed2005

Effects of the atypical antipsychotics olanzapine and risperidone on plasma prolactin levels in male rats: a comparison with clinical data.

RATIONALE: Hyperprolactinaemia is a common side effect of antipsychotic treatment and the clinical consequences associated with this, e.g. sexual dysfunction, can have a negative impact on patient compliance. OBJECTIVES: The aim of this study was to investigate the effect of the atypical antipsychotics olanzapine and risperidone on prolactin levels in rats using different treatment regimes and to compare these data with those reported clinically. METHODS: All experiments were carried out in male CD rats. In separate studies, the effects of acute, sub-chronic (7 days) and chronic (28 days) olanzapine and risperidone administration on prolactin levels were determined. Further studies investigated the time course of the prolactin response following olanzapine and risperidone treatment over 24 h. RESULTS: Both drugs significantly increased prolactin levels in a similar manner following acute administration, in keeping with clinically reported data. However, this elevation was still present following sub-chronic and chronic treatment, contrasting with clinical data with respect to olanzapine but not risperidone. Over 24 h, olanzapine demonstrated a more transient elevation of prolactin levels, whereas risperidone caused a robust and persistent increase in prolactin up to 24 h post-dose, closely mimicking clinical results. CONCLUSIONS: The present study has demonstrated that olanzapine and risperidone display similar effects on prolactin levels in the rat following acute and chronic administration but differ in their prolactin response over a 24-h period. In conclusion, prolactin levels in rats following atypical antipsychotic treatment may not be fully predictive of the clinical situation.

Animals↗

PubMed2005

In vitro immunoblockade of VIP inhibits the proliferation of pituitary prolactin cells.

VIP is a peptide synthesised in the pituitary gland and is involved in the stimulation of prolactin secretion. However, to date it has not been determined whether VIP is able to regulate the proliferation of pituitary prolactin-producing cells, like other factors involved in the regulation of prolactin such as estradiol or dopamine. The aim of the present study was to address whether VIP is involved in regulating the proliferation of pituitary prolactin-secreting cells. Thus, we performed an in vitro study on monolayer cultures of rat pituitary cells, neutralising the possible paracrine effect of VIP by immunoblockade of the peptide and later determining the degree of proliferation of prolactin-secreting cells. The effects of immunoblockade were validated by determining the levels of VIP in the culture media, which were decreased (P < 0.01), and modifications in the patterns of the immunohistochemical reaction to prolactin-positive cells. Immunoblockade of VIP decreased the proliferation of pituitary prolactin-positive cells at all antibody concentrations analysed, mainly between 3 and 12 h (P < 0.01). Moreover, immunoblockade decreased the sizes of the cellular and nuclear areas, except at 1 h, at which point it only decreased the nuclear area of prolactin-positive cells. The results obtained suggest that-in the same way as it regulates the secretion of the hormone-VIP could be involved in regulating the proliferation of prolactin cells, like estradiol or dopamine.

Animals↗

PubMed1985

Prolactin bioactivity following decidual synthesis and transport by amniochorion.

Current evidence suggests that high concentrations of prolactin in human amniotic fluid result from the transport of human decidual prolactin across reflected amniochorion. In this study, tritiated leucine placed on the isolated maternal side of amniochorion with adherent decidua was incorporated into newly synthesized tritiated human decidual prolactin. Identification of tritiated decidual prolactin on the fetal side of suspended membranes was confirmed within 4 hours of incubation. A heterologous species of human decidual prolactin identified on the maternal side of membranes was also detectable on the fetal side, and its bioactivity was found to be equivalent in both fetal and maternal chambers separated by amniochorion. These results confirm the de novo synthesis of human decidual prolactin and transport by amniochorion to the fetal side. Subsequent to transport, the biologic activity of human decidual prolactin is retained. Thus concentrations and biologic activity of amniotic-fluid prolactin can be accounted for by the transport of newly synthesized human decidual prolactin by the reflected amniochorion.

Amnion↗

PubMed1985

Inhibition of fetal membrane prostaglandin production by prolactin: relative importance in the initiation of labor.

Production of a biologically active prolactin by human decidual tissue and its influence on the permeability of amniochorion to water suggests a functional relationship between the polypeptide and fetal membrane metabolism. Under in vitro circumstances, we used ovine prolactin and the Ussing chamber technique to determine the role of prolactin in prostaglandin E2 production by human fetal membrane. Fresh reflected membranes obtained from elective cesarean sections were exposed to ovine prolactin (10 micrograms/ml). Aliquots of incubation media were sampled at 0, 30, 60, 120, and 240 minutes, quick-frozen, and later assayed for prostaglandin E2. Multifactorial analysis of variance revealed that ovine prolactin significantly reduced prostaglandin E2 production (f = 13.42, p less than 0.005). Prostaglandin E2 output was greatest by amnion (3581 +/- 596 pg/ml/gm declining to 1819 +/- 452 pg/ml/gm during 4 hours). Other combinations of fetal membranes including amnion-chorion-decidua produced only 12% to 15% prostaglandin E2 per gram compared with that produced by amnion alone. Those membranes similarly responded to prolactin with a reduction in prostaglandin E2 output of 34% to 59%. Correlation analysis identified a significant relationship between prostaglandin E2 production and time (r = 0.298; p less than 0.001), which was abolished by ovine prolactin (r = 0.115, p greater than 0.10). This model illustrates that ovine prolactin modifies the production of prostaglandin by fetal membranes in vitro. By analogy, endogenous prolactin by human decidual tissue might also inhibit the elaboration of prostaglandin E2 from its precursors residing within the fetal membranes.

Amnion↗

PubMed1989

Prolactin levels in umbilical cord blood of human infants: relation to gestational age, maternal complications, and neonatal lung function.

The ontogeny of serum prolactin and its relation to several variables, especially lung function, in 543 neonates was studied. Umbilical cord serum prolactin levels rose between 24 and 42 weeks' gestation, correlating significantly (p less than 0.001) with gestational age (r = 0.44) and birth weight (r = 0.32). Among infants of similar ages, however, there was no variation in serum prolactin level as a function of birth weight, sex, Apgar scores, or delivery method. Infants of women with pregnancy-induced hypertension had higher than normal prolactin levels; infants of diabetic women had normal prolactin levels. At 31.5 to 37 weeks' gestation, infants who developed respiratory distress syndrome had lower serum prolactin levels than those whose lung function was normal or else was abnormal from causes other respiratory distress syndrome. The risk for respiratory distress syndrome was higher in newborns whose prolactin level was low (10th percentile) than in infants whose prolactin level was high (90th percentile). These results are suggestive that prolactin may play a role in fetal lung maturation.

Apgar Score↗