Circulating Prolactin Levels Research Articles

The dopaminergic system in the brain of the native Thai chicken, Gallusdomesticus: Localization and differential expression across the reproductive cycle

Dopamine (DA) has a pivotal role in avian prolactin (PRL) secretion, acting centrally through D 1 DA receptors to stimulate PRL secretion by operating through vasoactive intestinal peptide (VIP). DA also inhibits PRL secretion by activating D 2 DA receptors at the pituitary level. This study was designed to investigate the distribution of DA neurons in the native Thai chicken, utilizing tyrosine hydroxylase (TH) as a marker for dopaminergic neurons. The differential expression of hypothalamic TH immunoreactive (TH-ir) neurons was also compared across the reproductive cycle. The results revealed that TH-ir neurons and fibers were found throughout the brain of the laying hen and were predominantly located within the diencephalon and mesencephalon. The observed distribution pattern of TH immunoreactivity was consistent with that reported previously in several avian species. However, changes in the number of TH-ir neurons in the nucleus intramedialis (nI) were observed across the reproductive cycle and correlated directly with variations in PRL levels. The population of TH-ir neurons in the nI increased significantly during the egg incubation period, where circulating PRL levels were the greatest. This study indicates, for the first time, that an association exists between DA neurons and the regulation of the reproductive system in the native Thai chicken. There is a paucity of information about the reproductive neuroendocrine regulation of tropical non-seasonally breeding avian species and it is suggested that the differential expression of DA neurons in the nI might play a role in the control of VIP secretion and subsequent PRL release in such birds.

Inhibition of prolactin secretion by American ginseng is mediated by ginseng polysaccharide‐induced nitric oxide production

Rats treated with American ginseng exhibit an approximate 50% reduction in serum prolactin levels and a compensatory decrease in hypothalamic dopamine activity. To investigate whether ginseng has direct pituitary effects, anterior pituitaries collected from random cycling female rats were dispersed and cultured for 1 week prior to treatment with water soluble ginseng extract (0 – 2 mg/ml) for 24 hr. Ginseng produced a dose‐dependent decrease in prolactin with maximum suppression (∼50%) within 6 hr at ≥1mg/ml; there was no change in media LH levels. When the ginsenoside and polysaccharide components in ginseng were examined, ginseng polysaccharides (12.5μg/ml) inhibited prolactin whereas ginsenosides had no effect in the pituitary cultures. Ginseng and its polysaccharides both stimulated nitric oxide (NO) production from cultured cells at 24 hr and induced iNOS gene and protein expression at 12 and 24 hr, respectively. The specific iNOS inhibitor 1400W blocked the ginseng/polysaccharide effects on NO production and prolactin release, whereas eNOS and nNOS inhibitors had no effect. Together, these results suggest that the reduction in circulating prolactin levels following ginseng ingestion is due to polysaccharide‐induced pituitary iNOS and NO production and subsequent prolactin suppression.

A comprehensive analysis of common genetic variation in prolactin (PRL) and PRL receptor (PRLR) genes in relation to plasma prolactin levels and breast cancer risk: the Multiethnic Cohort

BackgroundStudies in animals and humans clearly indicate a role for prolactin (PRL) in breast epithelial proliferation, differentiation, and tumorigenesis. Prospective epidemiological studies have also shown that women with higher circulating PRL levels have an increase in risk of breast cancer, suggesting that variability in PRL may also be important in determining a woman's risk.MethodsWe evaluated genetic variation in the PRL and PRL receptor (PRLR) genes as predictors of plasma PRL levels and breast cancer risk among African-American, Native Hawaiian, Japanese-American, Latina, and White women in the Multiethnic Cohort Study (MEC). We selected single nucleotide polymorphisms (SNPs) from both the public (dbSNP) and private (Celera) databases to construct high density SNP maps that included up to 20 kilobases (kb) upstream of the transcription initiation site and 10 kb downstream of the last exon of each gene, for a total coverage of 59 kb in PRL and 210 kb in PRLR. We genotyped 80 SNPs in PRL and 173 SNPs in PRLR in a multiethnic panel of 349 unaffected subjects to characterize linkage disequilibrium (LD) and haplotype patterns. We sequenced the coding regions of PRL and PRLR in 95 advanced breast cancer cases (19 of each racial/ethnic group) to uncover putative functional variation. A total of 33 and 60 haplotype "tag" SNPs (tagSNPs) that allowed for high predictability (Rh2 ≥ 0.70) of the common haplotypes in PRL and PRLR, respectively, were then genotyped in a multiethnic breast cancer case-control study of 1,615 invasive breast cancer cases and 1,962 controls in the MEC. We also assessed the association of common genetic variation with circulating PRL levels in 362 postmenopausal controls without a history of hormone therapy use at blood draw. Because of the large number of comparisons being performed we used a relatively stringent type I error criteria (p < 0.0005) for evaluating the significance of any single association to correct for performing approximately 100 independent tests, close to the number of tagSNPs genotyped for both genes.ResultsWe observed no significant associations between PRL and PRLR haplotypes or individual SNPs in relation to breast cancer risk. A nominally significant association was noted between prolactin levels and a tagSNP (tagSNP 44, rs2244502) in intron 1 of PRL. This SNP showed approximately a 50% increase in levels between minor allele homozygotes vs. major allele homozygotes. However, this association was not significant (p = 0.002) using our type I error criteria to correct for multiple testing, nor was this SNP associated with breast cancer risk (p = 0.58).ConclusionIn this comprehensive analysis covering 59 kb of the PRL locus and 210 kb of the PRLR locus, we found no significant association between common variation in these candidate genes and breast cancer risk or plasma PRL levels. The LD characterization of PRL and PRLR in this multiethnic population provide a framework for studying these genes in relation to other disease outcomes that have been associated with PRL, as well as for larger studies of plasma PRL levels.

Post-hatching parental care behaviour and hormonal status in a precocial bird

In birds, the link between parental care behaviour and prolactin release during incubation persists after hatching in altricial birds, but has never been precisely studied during the whole rearing period in precocial species, such as ducks. The present study aims to understand how changes in parental care after hatching are related to circulating prolactin levels in mallard hens rearing ducklings. Blood was sampled in hens over at least 13 post-hatching weeks and the behaviour of the hens and the ducklings was recorded daily until fledging. Contacts between hens and the ducklings, leadership of the ducklings and gathering of them steadily decreased over post-hatching time. Conversely, resting, preening and agonistic behaviour of hens towards ducklings increased. Plasma prolactin concentrations remained at high levels after hatching and then fell after week 6 when body mass and structural size of the young were close to those of the hen. Parental care behaviour declined linearly with brood age, showed a disruption of the hen-brood bond at week 6 post-hatching and was related to prolactin concentration according to a sigmoid function. Our results suggest that a definite threshold in circulating prolactin is necessary to promote and/or to maintain post-hatching parental care in ducks.

Prolactin-releasing peptide (PrRP) increases prolactin responses to TRH in vitro and in vivo

The Prolactin-releasing Peptide (PrRP) is a 31-aminoacid peptide produced and secreted from the hypothalamus, and postulated to promote the prolactin release from the pituitary. However, the action of PrRP remain controversial, since it was described to have potency comparable enough to TRH, although there are many evidences that PrRP is less potent than TRH. Here we have studied the effects of PrRP alone or in combination with TRH in the prolactin levels of rat pituitary primary cell cultures in vitro and also in vivo prolactin responses in randomly cycling and estrogens-treated female rats. PrRP itself increased prolactin levels in vitro and in vivo, although in a magnitude several times lower than TRH. In vivo PrRP promotes an atypical non-peaking progressive and maintained prolactin increase. On the other hand, PrRP markedly increased the prolactin responses to TRH in vitro (10-30 fold increase) and in vivo (up to three-fold increase). In addition, FGF-2 and EGF, two important growth factors present in the pituitary, reduced the PrRP-induced prolactin increase in vitro. Taken together our results suggest that PrRP released from the hypothalamus may be relevant to modulate the circulating prolactin levels in the rat.

Eucommia ulmoides Oliver as a Prophylactic against Restraint Stress in Water-induced Gastric Erosion in Rats

The aim of this study is to investigate the pharmacological effect of Eucommia ulmoides Oliv. and its components as prophylactics against restraint stress in water (RSW)-induced gastric erosion. In the test, an extract of E. ulmoides bark prepared using hot water was dissolved in water and used to assay its protective effect against gastric erosion in rats exposed to RSW for 7 h. Oral administration of the E. ulmoides extract (500 mg/kg per day) dissolved in 1 ml distilled water demonstrated a 44.9% protective effect against RSW-induced gastric erosion. The protective effect observed following the oral administration of the extract (50 and 500 mg/kg per day) for 2 weeks was dose-dependent. Oral administration of a 500 mg/kg dose of E. ulmoides extract increased the circulating prolactin (PRL) level and the expression level of the hypothalamic PRL receptor long form (PRLR(L)) mRNA in rats. Chlorogenic acid (CHA, 30 mg/kg per day) and geniposidic acid (GEA, 30 mg/kg per day), the major components of the E. ulmoides extract, showed a significant inhibitory effect on gastric erosion (20.9% and 21.8%, respectively) and an increase in the circulating PRL level and the expression level of the receptor mRNA in the hypothalamus. We showed that the protective effect of the E. ulmoides extract against gastric erosion may be partially due to the effects of CHA and GEA. E. ulmoides extract and its components enhance the circulating PRL level and stimulate hypothalamic PRLR(L) to produce an anti-stress effect. These results suggest that the PRLR(L)-driven actions in the hypothalamus that are induced by E. ulmoides extract and its components are important for coping with acute stress.

Effect of ethanol on 24-h hormonal changes in prolactin release mechanisms in growing male rats

This study analyzes the effect of chronic ethanol feeding on 24-h variation of hypothalamic-pituitary mechanisms involved in prolactin regulation in growing male Wistar rats. Animals were maintained under a 12:12 h light/dark photoperiod (lights off at 2000 h), and they received a liquid diet for 4 wk, starting on d 35 of life. The ethanol-fed group received a similar diet to controls except that maltose was isocalorically replaced by ethanol. Ethanol replacement provided 36% of the total caloric content of the diet. Rats were killed at six time intervals every 4 h, beginning at 0900 h. Mean concentration of serum prolactin in ethanol-fed rats was 58.7% higher than in controls. Peak circulating prolactin levels occurred at the early phase of the activity span in both groups of rats, whereas a second peak was found late in the resting phase in ethanol-fed rats only. In control rats, median eminence dopamine (DA), serotonin (5-HT), gamma-aminobutyric acid (GABA), and taurine levels exhibited two maxima, the major one preceding prolactin release and a second one during the first part of the resting phase. Median eminence DA and 5-HT turnover (as measured by 3,4-dihydroxyphenylacetic acid, DOPAC/DA, and 5-hydroxyindoleacetic acid, 5-HIAA/5-HT ratio) showed a single maximum preceding prolactin, at 0100 h. Ethanol treatment did not affect median eminence DA or 5-HT levels but it decreased significantly their turnover rate. The midday peak in DA and 5-HT levels (at 1300 h) was abolished and the night peak (at 0100 h) became spread and blunted in the ethanol-fed rats. This was accompanied with the disappearance of the 0100 h peak in DA and 5-HT turnover and the occurrence of a peak in 5-HT turnover at 1700 h. Ethanol intake suppressed the night peak in median eminence GABA and taurine (at 0100 h) as well as the midday peak of GABA. Ethanol augmented pituitary levels of DOPAC and 5-HIAA. The results indicate that chronic ethanol administration affects the mechanisms that modulate the circadian variation of prolactin release in growing male rats.

Potential Role of Thyroid Hormones and Prolactin in the Programming of Photorefractoriness in Turkey Hens

The domestic turkey hen is a seasonal breeder, requiring a period of short days to establish photosensitivity and a long day length to initiate egg production. The reproductive season is then limited by the onset of photorefractoriness (PR), which causes a decline, and then termination, of egg laying. In passerine birds, PR is programmed early in the reproductive season by the presence of thyroid hormones and a long photoperiod. High circulating prolactin (PRL) is thought to hasten the onset of PR. In a prior study, we reported that hens destined to have PR exhibited lower levels of thyroxine (T4) and PRL at certain points (weeks) following photostimulation than did hens destined to remain photosensitive (PS), a result opposite to what might be expected. The present study was conducted to further explore the possible relationship between circulating hormone levels and subsequent PR in the commercial turkey hen at times (days) closer to photostimulation than our previous study. Plasma levels of triiodothyronine (T3), T4, and PRL were compared in 2 subpopulations of hens identified retrospectively after 50 wk of egg production: A group of 17 hens that exhibited PR (mean onset = 27 wk of photostimulation) and a group of “good” layers that remained PS (mean production = 210 eggs/50 wk). Results showed no differences between groups in plasma T3 or T4 levels or in the T3:T4 ratio at −6, 0, 1, 3, and 7 d from photostimulation. Plasma PRL levels were significantly higher at 8 and 9 wk after photostimulation in hens that remained PS vs. those that became PR. We conclude that thyroid hormone levels around the time of photostimulation either are not actively related to programming of subsequent PR in turkeys or programming for PR in the turkey hen occurs later in the reproductive cycle than in passerine birds. We further conclude that hens that exhibit PR tend to have lower circulating PRL levels early in the reproductive season than hens that remain PS and lay at a relatively high rate.

The basal and TRH stimulated levels of prolactin in low risk climacteric patients with increased breast density: A matched pair case control trial

Objective To detect any significant alteration of basal and TRH stimulated circulating prolactin levels in those with an extremely dense breast composition as compared to ones with a fatty pattern in mammography in climacteric patients with a low risk probability for developing invasive breast cancer within five years according to a validated risk model. Materials and method In this matched pairs case-control trial a total of 67 climacteric patients with an extremely dense breast composition were compared to a control group of 71 climacteric patients with an almost entirely fat pattern composition in terms of basal and TRH stimulated circulating prolactin levels. All participants in the study had an estimated 5 years breast cancer risk less than 1.67% according to the validated model of Gail. Subgroup analysis was done according to menopausal status (premenopausal versus postmenopausal) and according to the hormone replacement therapy (HRT) in postmenopausal patients (current users of HRT versus never used HRT). Results We did not detect any statistically relevant differences between groups or subgroups in terms of basal, stimulated and Δ levels (stimulated-basal) of prolactin (ng/ml). The differences between groups of extremely dense composition versus almost fatty pattern in terms of ΔPRL (ng/ml) (±S.D.) were not statistically significant (68.1 ± 34.5 versus 69.1 ± 43.0; unpaired t test, Welch corrected p = 0.88, 95% CI −12.1 to 14.0). Conclusion Our results do not suggest a contribution of circulating prolactin to increased mammographic density in climacteric patients with low risk probability to develop breast cancer. A study of similar kind is warranted in high risk patients.

Physiologic Role for Prolactin Releasing Peptide

Prolactin (PRL) releasing peptide (PrRP) is produced in A1 and A2 catecholaminergic neurons of the ventrolateral medulla and nucleus tractus solitarius (NTS), respectively. PrRP-positive neurons in NTS project to the hypothalamic paraventricular and arcuate nuclei. I.c.v. administration of PrRP in conscious rats results in increased circulating PRL levels. We have developed an siRNA plasmid, which when injected bilaterally into the NTS results in significant diminution of immunoreactive PrRP content in the hypothalamus. We hypothesized that this would also impair the animal’s neuroendocrine response to restraint stress. Plasmid containing our PrRP siRNA or a control plasmid (scrambled siRNA) were injected bilaterally into the NTS of adult male rats bearing an indwelling jugular vein cannula. 18 hr later two blood samples (0 and 5 min) were withdrawn from the jugular cannula of conscious, unrestrained animals. They were then subjected to 10 min immobilization stress and additional blood samples taken during the stress (10 min) and at the end of the immobilization (15 min). The rats were then returned to their cages and two more blood samples taken at 20 and 30 min. There were no significant differences in plasma PRL levels between treatment groups before restraint (0 and 5 min). A significant, 10 fold increase in plasma PRL levels was observed in the control animals, while only a 4 fold increase in PRL was observed in siRNA treated rats. Plasma PRL levels were significantly lower in siRNA treated rats versus controls at 15, 20 and 30 min. These data demonstrate the efficacy of our plasmid based siRNA delivery system and suggest that PrRP, produced in neurons of the NTS which project to neuroendocrine centers in the hypothalamus, is an important mediator of stress related PRL secretion in the rat. Supported by NIH HL066023.

Suppression of prolactin does not reduce infant care by parentally experienced male common marmosets ( Callithrix jacchus)

High levels of prolactin have been found to correlate with the expression of paternal care in a variety of taxa. However, in mammals, there is little experimental evidence that prolactin is causally involved in the stimulation or maintenance of paternal care. Here, we suppressed prolactin production in paternally experienced common marmoset fathers in their family groups during the first 2 weeks after their infants were born. Circulating prolactin levels were suppressed using cabergoline (Dostinex: Pfizer), a long acting dopamine (D 2) agonist with minimal behavioural side-effects. A within-subject design was used to compare behavioural and hormonal data on 5 paternally experienced fathers during two consecutive births. Cabergoline reduced prolactin to negligible levels in all fathers without effecting testosterone, DHT and cortisol and without adverse side-effects. However, lowering prolactin had no significant effect on the expression of majority of the behaviour patterns associated with paternal care. These included infant carrying, infant grooming and the frequency with which fathers retrieved and rejected infants. The only infant-related behaviour to be affected was the frequency with which fathers touched, licked and investigated infants. We noted a marginally significant increase in this behaviour during cabergoline treatment. Despite the lack of effect on paternal care, cabergoline did exert an effect on the affiliative/sexual behaviour of fathers as there was a significant increase in the grooming behaviour fathers directed at and received from their mates during drug treatment. This study showed that experienced male marmosets can express paternal behaviour in the absence of the high prolactin levels normally seen after infants are born.

Perinatal Glucocorticoid Treatment Disrupts the Hypothalamo-Lactotroph Axis in Adult Female, But Not Male, Rats

This study aimed to test the hypothesis that the tuberoinfundibular dopaminergic neurons of the arcuate nucleus and/or the lactotroph cells of the anterior pituitary gland are key targets for the programming effects of perinatal glucocorticoids (GCs). Dexamethasone was administered noninvasively to fetal or neonatal rats via the mothers' drinking water (1 mug/ml) on embryonic d 16-19 or neonatal d 1-7, and control animals received normal drinking water. At 68 d of age, the numbers of tyrosine hydroxylase-positive (TH+) cells in the arcuate nucleus and morphometric parameters of pituitary lactotrophs were analyzed. In control animals, striking sex differences in TH+ cell numbers, lactotroph cell size, and pituitary prolactin content were observed. Both pre- and neonatal GC treatment regimens were without effect in adult male rats, but in females, the overriding effect was to abolish the sex differences by reducing arcuate TH+ cell numbers (pre- and neonatal treatments) and reducing lactotroph cell size and pituitary prolactin content (prenatal treatment only) without changing lactotroph cell numbers. Changes in circulating prolactin levels represented a net effect of hypothalamic and pituitary alterations that exhibited independent critical windows of susceptibility to perinatal GC treatments. The dopaminergic neurons of the hypothalamic periventricular nucleus and the pituitary somatotroph populations were not significantly affected by either treatment regimen in either sex. These data show that the adult female hypothalamo-lactotroph axis is profoundly affected by perinatal exposure to GCs, which disrupts the tonic inhibitory tuberoinfundibular dopaminergic pathway and changes lactotroph morphology and prolactin levels in the pituitary and circulation. These findings provide new evidence for a long-term disruption in prolactin-dependent homeostasis in females, but not males, after inappropriate GC exposure in perinatal life.

Experimental allergic encephalomyelitis in pituitary-grafted Lewis rats.

Treatment of susceptible rats with dopaminergic agonists that reduce prolactin release decreases both severity and duration of clinical signs of experimental allergic encephalomyelitis (EAE). To assess to what extent the presence of an ectopic pituitary (that produces an increase in plasma prolactin levels mainly derived from the ectopic gland) affects EAE, 39 male Lewis rats were submitted to pituitary grafting from littermate donors. Another group of 38 rats was sham-operated by implanting a muscle fragment similar in size to the pituitary graft. All rats received subcutaneous (s.c.) injections of complete Freund's adjuvant (CFA) plus spinal cord homogenate (SCH) and were monitored daily for clinical signs of EAE. Animals were killed by decapitation on days 1, 4, 7, 11 or 15 after immunization and plasma was collected for prolactin RIA. In a second experiment, 48 rats were immunized by s.c. injection of a mixture of SCH and CFA, and then received daily s.c. injections of bromocriptine (1 mg/kg) or saline. Groups of 8 animals were killed on days 8, 11 or 15 after immunization and plasma prolactin was measured. Only sham-operated rats exhibited clinical signs of the disease when assessed on day 15 after immunization. A progressive decrease in plasma prolactin levels was observed in pituitary-grafted rats, attaining a minimum 15 days after immunization, whereas plasma prolactin levels were increased during the course of the disease in sham-operated rats. Plasma prolactin levels were higher in pituitary-grafted rats than in sham-operated rats 1 day after immunization, but lower on days 7, 11 and 15 after immunogen injection. Further supporting a correlation of suppressed prolactin levels with absence of clinical signs of EAE, rats that were administered the dopaminergic agonist bromocriptine showed very low plasma prolactin levels and did not exhibit any clinical sign of EAE. These results indicate that low circulating prolactin levels coincide with absence of clinical signs of EAE in Lewis rats.

Testis Structure and Function in a Nongenetic Hyperadipose Rat Model at Prepubertal and Adult Ages

There are few data for hormonal levels and testis structure and function during postnatal development in rats neonatally treated with monosodium L-glutamate (MSG). In our study, newborn male pups were ip injected with MSG (4 mg/g body weight) every 2 d up to 10 d of age and investigated at prepubertal and adult ages. Plasma levels of leptin, LH, FSH, prolactin, testosterone (T), corticosterone, and free T4 (FT4) were measured. MSG rats displayed elevated circulating levels of corticosterone and hyperadiposity/hyperleptinemia, regardless of the age examined; conversely, circulating prolactin levels were not affected. Moreover, prepubertal MSG rats revealed a significant (P < 0.05) reduction in testis weight and the number of Sertoli (SC) and Leydig cells per testis. Leptin plasma levels were severalfold higher (2.41 vs. 8.07; P < 0.05) in prepubertal MSG rats, and these animals displayed plasma LH, FSH, T, and FT4 levels significantly decreased (P < 0.05). Taken together, these data indicate that testis development, as well as SC and Leydig cell proliferation, were disturbed in prepubertal MSG rats. Adult MSG rats also displayed significantly higher leptin plasma levels (7.26 vs. 27.04; P < 0.05) and lower (P < 0.05) LH and FSH plasma levels. However, T and FT4 plasma levels were normal, and no apparent alterations were observed in testis structure of MSG rats. Only the number of SCs per testis was significantly (P < 0.05) reduced in the adult MSG rats. In conclusion, although early installed hyperadipose/hyperleptinemia phenotype was probably responsible for the reproductive axis damages in MSG animals, it remains to be investigated whether this condition is the main factor for hypothalamus-pituitary-gonadal axis dysfunction in MSG rats.

Disparate release of prolactin and growth hormone from the tilapia pituitary in response to osmotic stimulation

In most teleost fishes, prolactin (PRL) plays a key role in freshwater (FW) adaptation, whereas growth hormone (GH) is involved in seawater (SW) adaptation in salmonids and certain euryhaline species including the tilapia, Oreochromis mossambicus. Consistent with its osmoregulatory activity, PRL release increases in response to physiologically relevant reductions in extracellular osmolality. When dispersed PRL and GH cells from FW-acclimatized fish were incubated in media of varying osmolalities, PRL release increased significantly in response to a 12% reduction in medium osmolality during 1 and 4 h of exposure. By contrast, cells from SW-acclimatized fish responded only to a 24% reduction in osmolality. Growth hormone release on the other hand increased whether medium osmolality was reduced or raised. Cell volume increased together with PRL release during the perifusion of dispersed PRL cells in direct proportion to the reduction in medium osmolality. Growth hormone release increased whether GH cell volume increased or decreased. In in vivo studies, circulating PRL levels increased as early as 1 h after the transfer of fish from SW to FW, whereas GH levels remained unchanged during 24 h of acclimatization. These results indicate that while PRL and GH cells are osmosensitive, the PRL cells respond to reductions in extracellular osmolality in a manner that is consistent with PRL’s physiological role in the tilapia. While the rise in GH release following the reduction in osmolality is of uncertain physiological significance, the rise in GH release with the elevation of medium osmolality may be connected to its role in SW adaptation.

Steroid-induced alterations in mRNA expression of the long form of the prolactin receptor in the medial preoptic area of female rats: Effects of exposure to a pregnancy-like regimen of progesterone and estradiol

It is firmly established that the onset of maternal behavior in the female rat is stimulated by a combination of hormones that include prolactin (PRL), estradiol (E 2), and progesterone (P 4). Specifically, nulliparous rats display short latencies to respond to foster young when primed with Silastic capsules filled with P 4 and E 2 and then administered PRL centrally to the medial preoptic area (MPOA), an area integrally involved in the expression of maternal behavior in this species. PRL or P 4 treatments alone are ineffective in stimulating the expression of maternal care. Since the actions of PRL in the MPOA appear to be mediated by PRL receptors, it was of interest to determine whether and how treatment with P 4 and E 2 together or separately might alter mRNA expression of the long form of the PRL receptor (PRL-R L) in the MPOA. Using in situ hybridization histochemistry (ISHH), mRNA expression of the PRL-R L was measured in the MPOA of ovariectomized, nulliparous rats treated with various combinations of P 4 and E 2. Treatment of animals with P 4 alone for 10 days or with P 4 followed by E 2 for 1 or 4 days resulted in reductions in PRL receptor mRNA expression in the MPOA when compared with the expression in animals treated with E 2 alone or blank capsules. The actions of P 4 on mRNA expression of the PRL-R L were more pronounced in the dorsal MPOA. Circulating PRL levels collected at the time of sacrifice were elevated in all groups treated with E 2, but no association between PRL levels and receptor mRNA expression within the MPOA was evident. These findings indicate that the dorsal MPOA may be one site of progesterone's action in facilitating prolactin-mediated maternal behavior.

A case of systemic lupus erythematosus: continued association of circulating prolactin levels with disease activity over a 4-year follow-up period

Circulating prolactin levels in a woman with systemic lupus erythematosus (SLE) were measured over a period of 4 years, and her hyperprolactinemia remained associated with disease activity throughout. Circulating prolactin could thus be a better practical marker than standard parameters such as anti-double-stranded DNA antibodies and serum complement in some patients with SLE.

The relative importance of vasoactive intestinal peptide and peptide histidine isoleucine as physiological regulators of prolactin in the domestic turkey

In mammals, prolactin (PRL) secretion is regulated by vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI). In birds, however, VIP is considered a PRL-releasing factor (PRF), while the role of PHI is unknown. The purpose of this study was to compare the effects of turkey PHI (tPHI) and turkey VIP (tVIP) on PRL secretion in vitro, and to study their physiological significance in vivo through active immunization against tPHI and tVIP. In vitro studies were conducted using pituitary cell cultures from female turkeys. In the in vivo study, female turkeys were immunized with keyhole limpet hemocyanin (KLH; control), synthetic tPHI conjugate (KLH–tPHI), or synthetic tVIP conjugate (KLH–tVIP). Both tVIP and tPHI stimulated PRL secretion from anterior pituitary cells in a dose response manner. However, tPHI was 100-fold less potent than tVIP in stimulating maximum PRL secretion in vitro. In addition, the highest dose (10 −4 M) of tPHI inhibited its own PRL-releasing activity as well as that of VIP-stimulated PRL release. Whereas, circulating PRL levels and nesting activity remained low and unchanged during the photo-induced reproductive cycle (i.e., experimental period) in tVIP-immunized birds, control and tPHI-immunized turkeys showed a significant increase in plasma PRL levels and in the incidence of incubation behavior over time following photostimulation. These findings, taken together with earlier results, indicate that VIP is the sole physiological PRF in the turkey (avian species).

Prolactin daily rhythm in suckling male rabbits.

BackgroundThis study describes the 24-h changes in plasma prolactin levels, and dopamine (DA), serotonin (5HT), gamma-aminobutyric acid (GABA) and taurine concentration in median eminence and adenohypophysis of newborn male rabbits.MethodsAnimals were kept under controlled light-dark cycles (LD 16:8, lights on at 08:00 h), housed in individual metal cages, and fed ad libitum with free access to tap water. On day 1 after parturition, litter size was standardized to 8–9 to assure similar lactation conditions during the experiment. Groups of 6–7 suckling male rabbits were killed by decapitation on day 11 of life at six different time points during a 24-h period.ResultsPlasma prolactin levels changed significantly throughout the day, showing a peak at the beginning of the active phase (at 01:00 h) and a second maximum during the first part of the resting phase (at 13:00 h). Median eminence DA concentration also changed significantly during the day, peaking at the same time intervals as plasma prolactin. A single maximum (at 13:00 h) was found for adenohypophysial DA concentration. Individual adenohypophysial DA concentrations correlated significantly with their respective plasma prolactin levels. A maximum in median eminence 5HT concentration occurred at 21:00 h whereas adenohypophysial 5HT peaked at 13:00 h. Median eminence 5HT concentration and circulating prolactin correlated inversely. In the median eminence, GABA concentration attained maximal values at 21:00 h, whereas it reached a maximum at 13:00 h in the pituitary gland. Median eminence GABA concentration correlated inversely with circulating prolactin. In the median eminence, taurine values varied in a bimodal way showing two maxima, at the second half of the rest span and of the activity phase, respectively. In the adenohypophysis, minimal taurine levels coincided with the major plasma prolactin peak (at 01:00 h). Circulating prolactin and adenohypophysial taurine levels correlated inversely.ConclusionThe correlations among the changes in the neurotransmitters analyzed and circulating prolactin levels explain the circadian secretory pattern of the hormone in newborn male rabbits.

Toxic effects of cadmium on the regulatory mechanism of dopamine and serotonin on prolactin secretion in adult male rats

This work was designed to analyze the effects of cadmium on the regulatory mechanism of prolactin in cadmium-exposed rats. Adult male rats were given cadmium at a dose of 25 ppm of cadmium chloride (CdCl 2) in the drinking water for 1 month. At the end of the treatment, the rats were killed at six different time intervals throughout a 24 h cycle to measure circulating prolactin levels and dopamine and serotonin content in the median eminence and in both anterior and posterior pituitary. Control and cadmium-exposed animals exhibited significant time of day-dependent variations in plasma prolactin levels and in dopamine and serotonin concentration in all analyzed tissue. Cadmium exposure did not modify the mean values of the hormone around the clock but it modified the amplitude of the secretory peaks at 08:00 and 12:00 h. Cadmium decreased dopamine content in the median eminence, while increased its content in the posterior pituitary and induced a phase advanced peak at 20:00 h. On the other hand, serotonin content was not modified in the median eminence. Only differences in specific time points were observed, while serotonin concentration in anterior and posterior pituitary were increased in cadmium-treated rats. Differences in time peaks were also observed. The negative correlation between plasma prolactin and dopamine content in pituitary, and between plasma levels of the hormone and serotonin content in posterior pituitary, disappeared in cadmium-treated animals.