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PubMed2006

Prolactin and breast cancer risk.

Prolactin, a hormone involved in normal breast development and lactation, has been hypothesized to be important in the etiology of breast cancer. This review summarizes in vitro, animal, and epidemiologic data supporting this hypothesis. Experimental evidence indicates that prolactin can promote cell proliferation and survival, increase cell motility, and support tumor vascularization. Animal data suggest that prolactin can increase tumor growth rates and the number of metastases, as well as induce both estrogen receptor +(ER) and ER--tumors in a transgenic mouse model in which ER+ tumors are very rare. Epidemiologic data for premenopausal women are sparse; however a recent study with 235 cases reported a significant positive association between plasma prolactin levels and breast cancer risk. Studies in postmenopausal women have reported a positive association as well, and in the largest study (n=851 cases) the association was strongest for ER+ tumors. Overall, the available data support the hypothesis that prolactin increases risk of breast cancer. Future research directions include better characterizing the potential interplay between prolactin and estrogen and determining whether genetic variability in prolactin-related genes is associated with breast cancer risk.

Animals↗
PubMed2006

Elevated prolactin serum levels and history of alcohol withdrawal seizures.

BACKGROUND: Prolactin has been discussed to be useful for differential diagnosis in epilepsia. Aim of the present study was to investigate the association between prolactin serum levels and previous alcohol withdrawal seizures. METHODS: We assessed 118 male patients admitted for detoxification treatment. Previous withdrawal seizures were recorded and prolactin serum levels were measured using an enzymatic immunoassay. RESULTS: Patients with a history of alcohol withdrawal seizures had significantly higher prolactin levels (17.8 ng/ml, SD=12.1) than patients without previous seizures (13.0 ng/ml, SD=8.1, p<0.05). Logistic regression revealed significant predictive qualities for prolactin serum levels (B=0.05, Wald=5.30, p=0.021, OR=1.06, 95%CI=1.01-1.11). CONCLUSIONS: The present findings show an association between elevated prolactin serum levels and a history of withdrawal seizures. Hence, the results suggest that prolactin elevation at admission may be a clinical marker for an increased risk of withdrawal seizures.

Adult↗
PubMed2005

Lack of involvement of dopamine and serotonin during the orphanin FQ/Nociceptin (OFQ/N)-induced prolactin secretory response.

The purpose of these studies was to examine possible mechanisms of Orphanin FQ/Nociceptin (OFQ/N)-induced prolactin release. We investigated the involvement of the dopaminergic neurons by quantifying DOPAC:DA levels in the median eminence and neurointermediate lobe following central administration of OFQ/N to female Sprague-Dawley rats. To specifically determine the involvement of the tuberoinfundibular dopaminergic neurons, immunocytochemical studies were conducted to visualize c-fos protein expression in the arcuate nucleus following central administration of OFQ/N. In addition, the role of serotonergic activation was examined in dose response studies using the selective serotonin antagonist ritansarin and the nonselective antagonist metergoline. Finally, the pharmacological specificity of the prolactin response was examined by pretreating animals with [Nphe1] NC (1-13)NH2, a drug reported to antagonize OFQ/N effects. The results of these studies indicate that the increase in prolactin release following central administration of OFQ/N does not inhibit tuberoinfundibular, tuberohypophyseal or periventricular hypophysial dopaminergic neuronal activity at 10 min after drug administration, a time when prolactin levels were significantly elevated. Furthermore, serotonergic activation is not involved since pharmacological blockade of serotonergic receptors did not alter the prolactin secretory response to OFQ/N. NC (1-13)NH2 did not antagonize the stimulatory effects of OFQ/N on prolactin secretion. The neural effects of OFQ/N on dopaminergic neuronal activity may occur following a different time course than that of the prolactin increase.

Animals↗
PubMed2005

Urinary prolactin is correlated with mothering and allo-mothering in squirrel monkeys.

The hormone prolactin is implicated in infant care-giving by parents and allo-parents in a variety of species. Adult female squirrel monkeys (Saimiri spp.) engage in allo-mothering behavior, which includes carrying and nursing infants, but communal care of offspring has not been investigated from an endocrine standpoint in this taxon. We attempted to fill this gap by examining prolactin levels in squirrel monkeys (Saimiri sciureus) as a function of parental responsiveness. Subjects were housed at the National Institutes of Health Animal Center and assays were performed at the Wisconsin National Primate Research Center. To test for the presence of prolactin in squirrel monkey, saliva, blood and saliva were simultaneously collected from anesthetized subjects during routine health examinations. Prolactin was detectable in serum but not in saliva samples. In the core investigation, behavioral data were collected by focal animal sampling on three 1-male multi-female groups, and individually identified urine was collected non-invasively from foil containers underneath group cages on a daily basis throughout the behavioral study. Changes in urinary prolactin over time reflected changes in the reproductive state of a female who was pregnant, gave birth and lactated during the study. Mean urinary prolactin levels in non-lactating females and a male housed with infants in one group were higher than in adults from 2 groups without infants. In the group with infants, mean urinary prolactin levels in adults increased with the amount of infant contact and care-giving. The squirrel monkey may represent a new primate model for investigating the endocrinology of infant care-giving.

Age Factors↗
PubMed2005

Effects of the dopamine agonist cabergoline on the pulsatile and TRH-induced secretion of prolactin, LH, and testosterone in male beagle dogs.

In the present study, the pulsatile serum profiles of prolactin, LH and testosterone were investigated in eight clinically healthy fertile male beagles of one to six years of age. Serum hormone concentrations were determined in blood samples collected at 15 min intervals over a period of 6 h before (control) and six days before the end of a four weeks treatment with the dopamine agonist cabergoline (5 microg kg(-1) bodyweight/day). In addition, the effect of cabergoline administration was investigated on thyrotropin-releasing hormone (TRH)-induced changes in the serum concentrations of these hormones. In all eight dogs, the serum prolactin concentrations (mean 3.0 +/- 0.3 ng ml(-1)) were on a relatively constant level not showing any pulsatility, while the secretion patterns of LH and testosterone were characterised by several hormone pulses. Cabergoline administration caused a minor but significant reduction of the mean prolactin concentration (2.9 +/- 0.2 ng ml(-1), p < 0.05) and did not affect the secretion of LH (mean 4.6 +/- 1.3 ng ml(-1) versus 4.4 +/- 1.7 ng ml(-1)) or testosterone (2.5 +/- 0.9 ng ml(-1) versus 2.4 +/- 1.2 ng ml(-1)). Under control conditions, a significant prolactin release was induced by intravenous TRH administration (before TRH: 3.8 +/- 0.9 ng ml(-1), 20 min after TRH: 9.1 +/- 5.9 ng ml(-1)) demonstrating the role of TRH as potent prolactin releasing factor. This prolactin increase was almost completely suppressed under cabergoline medication (before TRH: 3.0 +/- 0.2 ng ml(-1), 20 min after TRH: 3.3 +/- 0.5 ng ml(-1)). The concentrations of LH and testosterone were not affected by TRH administration. The results of these studies suggest that dopamine agonists mainly affect suprabasal secretion of prolactin in the dog.

Administration, Oral↗
PubMed2006

Prolactin and growth hormone in fish osmoregulation.

Prolactin is an important regulator of multiple biological functions in vertebrates, and has been viewed as essential to ion uptake as well as reduction in ion and water permeability of osmoregulatory surfaces in freshwater and euryhaline fish. Prolactin-releasing peptide seems to stimulate prolactin expression in the pituitary and peripheral organs during freshwater adaptation. Growth hormone, a member of the same family of hormones as prolactin, promotes acclimation to seawater in several teleost fish, at least in part through the action of insulin-like growth factor I. In branchial epithelia, development and differentiation of the seawater-type chloride cell (and their underlying biochemistry) is regulated by GH, IGF-I, and cortisol, whereas the freshwater-type chloride cell is regulated by prolactin and cortisol. In the epithelia of gastrointestinal tract, prolactin induces cell proliferation during freshwater adaptation, whereas cortisol stimulates both cell proliferation and apoptosis. We propose that control of salinity acclimation in teleosts by prolactin and growth hormone primarily involves regulation of cell proliferation, apoptosis, and differentiation (the latter including upregulation of specific ion transporters), and that there is an important interaction of these hormones with corticosteroids.

Acclimatization↗
PubMed2006

Cloning and sequence analysis of pituitary prolactin cDNA from the northern brown bandicoot (Isoodon macrourus).

The nucleotide sequence for pituitary prolactin cDNA from the marsupial bandicoot (Isoodon macrourus) was determined by reverse transcription-polymerase chain reaction and 5'/3' rapid amplification of cDNA ends. The deduced amino acid sequence showed high sequence identity with brushtail possum prolactin (95%) and all of the expected structural features of a quadruped prolactin. A prolactin gene tree was constructed and rates of evolution calculated for bandicoot, possum, opossum and several mammalian and non-mammalian prolactins. Bootstrap analysis provided strong support for marsupials as a sister group with eutherian mammals and weak support for opossum and bandicoot as an independent grouping from the brushtail possum. The rates of molecular evolution for marsupial prolactins were comparable to the slow rate seen in the majority of quadruped prolactins that have been sequenced.

Amino Acid Sequence↗
PubMed2004

Prolactin-induced parental hyperphagia in ring doves: are glucocorticoids involved?

Hyperphagia is a prominent component of the parental behavior repertoire in male and female ring doves and is necessary in order for parents to successfully provision their growing young. Although previous studies implicate both prolactin and the endogenous glucocorticoid, corticosterone, in parental hyperphagia, the functional interactions between these two hormones in regulating changes in feeding activity have not been characterized. These studies examined the possibility that prolactin's orexigenic effects are mediated through the increased secretion of corticosterone. Twice-daily intracerebroventricular (icv) injection of prolactin increased plasma corticosterone concentration in non-breeding doves of both sexes, with males exhibiting more pronounced effects than females. To further test the importance of glucocorticoid signaling in prolactin-induced feeding responses, changes in food intake were investigated in icv prolactin-treated, non-breeding doves following icv infusion of the glucocorticoid receptor antagonist RU38486 or propylene glycol vehicle. No attenuation of prolactin-induced hyperphagia was observed in either sex following co-administration of RU38486 at a dose shown previously to block dexamethasone-induced feeding in doves. These findings suggest that elevated corticosterone titers in blood may contribute to the hyperphagia observed in response to prolactin, but corticosterone signaling through a mammalian-type glucocorticoid receptor is not essential.

Animals↗
PubMed2006

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 (D2) 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.

Animals↗
PubMed1993

Role of melatonin in nocturnal prolactin secretion in women with normoprolactinemia and mild hyperprolactinemia.

OBJECTIVE: Our objective was to clarify the relationship between the nocturnal melatonin surge and the nocturnal prolactin release in women with normoprolactinemia and mild hyperprolactinemia. STUDY DESIGN: Nocturnal serum melatonin and prolactin levels were determined for a various awake/sleep and light/dark conditions in a total of 23 healthy normoprolactinemia and 9 mild hyperprolactinemia. Patterns of prolactin and melatonin levels were subject to analysis of variance. RESULTS: During sleep deprivation under continuous illumination in normoprolactinemia, neither melatonin nor prolactin increased in concentration. In contrast, during sleep deprivation in a dark environment, both hormones were increased. The maximal prolactin levels in mild hyperprolactinemia under physiologic sleep/dark were significantly higher (p < 0.01) and were reached 2 hours earlier than in normoprolactinemia. However, each woman with mild hyperprolactinemia had similar melatonin surges. Oral administration (1 mg) of melatonin to normoprolactinemia and mild hyperprolactinemia in the daytime resulted in release of prolactin in a fashion similar to that observed during the night. CONCLUSION: Melatonin can regulate nocturnal prolactin secretion independent of sleep-related factors. Furthermore, the nature of the response to exogenous melatonin administration suggests that mild hyperprolactinemia may be unusually sensitive to melatonin.

Adult↗
PubMed1977

Decidua: a possible source of amniotic fluid prolactin.

The source of amniotic fluid prolactin was investigated with the use of amnion, chorion, placenta, and decidual tissue taken from term human pregnancy. Decidua alone of these tissues contained significant quantities of prolactin. The release of decidual prolactin was affected by the presence or absence of oxygen and protein, and the amount of prolactin released far exceeded the decrease in tissue content during incubation. It is concluded that: (1) decidua may be a major source of amniotic fluid prolactin, (2) synthesis of prolactin occurs during incubation of decidua, and (3) sufficient prolactin is present in the decidua to account for that found in amniotic fluid at term.

Amnion↗
PubMed1987

Modulating actions of estradiol on gonadotropin-releasing hormone-stimulated prolactin secretion in postmenopausal individuals.

The temporal aspects of estrogen treatment on serum prolactin concentrations basally and in response to a 10 micrograms intravenous injection of gonadotropin-releasing hormone were assessed in eight postmenopausal women. The response of prolactin to gonadotropin-releasing hormone stimulation was compared with that of follicle-stimulating hormone and luteinizing hormone obtained simultaneously. Basal serum prolactin increased significantly (p less than 0.001) in response to estrogen treatment, and a positive correlation was found between the serum concentrations of estradiol and prolactin (r2 = 0.266; p = 0.0011). Gonadotropin-releasing hormone induced a significant increase in serum prolactin concentrations, which was greater after 5 to 10 days of estrogen treatment compared with that in the estrogen-depleted state (p = 0.031). No correlation was found between gonadotropin-releasing hormone-stimulated prolactin and luteinizing hormone or follicle-stimulating hormone release. These data demonstrate that estrogen treatment of previously hypoestrogenemic postmenopausal women potentiates gonadotropin-releasing hormone-stimulated prolactin release. Furthermore, our data suggest that the previously described paracrine interaction between the gonadotropins and lactotropes exerted by gonadotropin-releasing hormone does not appear to be mediated via increased gonadotropin release.

Estradiol↗
PubMed1986

Prolactin administration stimulates rat hepatic DNA synthesis.

Prolactin is an important growth modulatory hormone in fetal and adult tissues. Its administration stimulates enzymatic markers of the G1 phase of cell cycle in rat liver and other tissues. To determine the effects of prolactin administration on hepatic DNA synthesis (S phase), rats received prolactin at 12 hour intervals for 48 hours and DNA synthesis was assessed by [3H]-thymidine incorporation. Prolactin administration stimulated DNA synthesis 2-4 fold above controls in the livers of adult and weanling animals. Increased incorporation of radiolabel was associated with the nucleus of hepatoparenchymal cells. These data support the hypothesis that prolactin may be a physiological regulator of hepatic DNA synthesis. Further, since stress stimulates prolactin secretion, we suggest that prolactin may participate in the hepatic compensatory hyperplasia elicited by the stress associated with partial hepatectomy.

Age Factors↗
PubMed1979

Relationship between plasma prolactin and the endocrine microenvironment of the developing human antral follicle.

The aim of the present study was to determine whether any obvious relationships exist between the circulating levels of prolactin at the time of ovariectomy and the endocrine microenvironment and developmental status of antral follicles. The concentrations of prolactin, follicle-stimulating hormone (FSH), and estradiol were measured in peripheral plasma and in antral fluid of follicles collected at varying stages of the menstrual cycle. In addition, the granulosa cells were recovered from each follicle (greater than or equal to 4 mm in diameter) and their numbers were quantitated. When the plasma levels of prolactin ranged from 11 to 100 ng/ml, the antral fluid levels of prolactin were uniformly low (less than 20 ng/ml) and the over-all level of intrafollicular activity remained unchanged. However, when the prolactin concentrations in plasma exceeded 100 ng/ml, the levels of prolactin in antral fluid were significantly elevated. Moreover, the high levels of intrafollicular prolactin were associated with a marked reduction in FSH accumulation and low levels of estradiol in antral fluid. Also, these follicles were severely deficient in granulosa cells. This marked reduction in intrafollicular activity was not associated with any significant changes in the mean levels of estradiol and FSH in peripheral plasma. These findings suggest that hyperprolactinemia is associated with a marked reduction in intraovarian activity and that the extent of this reduction may not be always apparent from the levels of circulating estradiol.

Adult↗
PubMed1981

Mechanisms of control of prolactin release in response to apprehension stress and anesthesia-surgery stress.

The response of prolactin to stress may not be controlled by a single mechanism. This study was designed to measure the prolactin response in the human female to two reproducible stresses: the apprehension (A) prior to surgery (laparoscopy and hysteroscopy) and the stress of the anesthesia-surgery (AS). Attempts to modify the release of prolactin was made by pharmacologic means. Thirty-eight normally menstruating women served either as controls or received histamine (H1), serotonin, opioid, or dopamine receptor-blocking agents and the prolactin response was measured. The release of prolactin to AS was blunted by higher-dose of opioid and by dopamine antagonists. The A release of prolactin was enhanced by the dopaminergic antagonist and blunted by the other three agents. It was concluded that the mechanism for the stress-induced release of prolactin may vary depending upon the nature of the stress.

Adult↗
PubMed1997

Suppression of luteal phase, but not midcycle, prolactin levels by chronic follicular phase opiate antagonism.

OBJECTIVE: To investigate whether establishment and maintenance of chronic opioid blockade throughout the follicular phase of the menstrual cycle influences midcycle and luteal phase prolactin levels. DESIGN: Randomized, double-blind, crossover study. SETTING: Academic research environment. PATIENT(S): Volunteers, aged 21-35 years, with regular menstrual cycles. INTERVENTION(S): Naltrexone (50 mg) or placebo were administered on cycle days 2-14. Blood samples were obtained in the early follicular phase and in the periovulatory and midluteal phases of the menstrual cycle. MAIN OUTCOME MEASURE(S): Serum prolactin levels. RESULT(S): In the early follicular phase, serum prolactin levels were equivalent in naltrexone (12.0 +/- 2.7 microgram/L; mean +/- SE) and placebo (12.1 +/- 2.9 micrograms/L) cycles. A statistically significant increase in serum prolactin was observed on the day of the LH surge (naltrexone: 22.6 +/- 3.7 micrograms/L; placebo: 21.7 +/- 2.7 micrograms/L; P < 0.05 versus early follicular phase), but no difference between treatments was observed. However, midluteal prolactin levels were statistically significantly lower in naltrexone cycles compared with placebo cycles (12.6 +/- 3.3 versus 15.4 +/- 3.0 micrograms/L; P < 0.05). CONCLUSION(S): Chronic blockade of opioid activities during the follicular phase does not affect midcycle prolactin increments, but withdrawal of opioid blockade may enhance opioid effects on prolactin levels in the luteal phase.

Adult↗
PubMed1997

Cervicovaginal washing prolactin assay in prediction of preterm delivery.

OBJECTIVE: Our purpose was to determine the utility of cervicovaginal washing prolactin assay in prediction of preterm birth in women without rupture of membranes. METHODS: Sixty-six women with normal singleton pregnancy were submitted to cervicovaginal washing and serum prolactin assays. The latency period to delivery and gestational age at admission and at delivery were also recorded. According to uterine contractions and obstetrical history regarding the previous preterm delivery, the pregnant women were divided into 4 groups: 18 symptomatic (group 1) and 15 asymptomatic (group 2) pregnancies who had previously had preterm delivery, and 18 symptomatic (group 3) and 15 asymptomatic (group 4) pregnancies without a history of prior preterm delivery were enrolled in the study. RESULTS: The cervicovaginal washing prolactin concentrations were significantly higher in groups 1 and 3 than in group 4 (P < 0.0083). With respect to the latency period to delivery and the birth weeks, groups 2 and 4 were significantly higher than groups 1 and 3 (F < 0.0001). In the evaluation of the whole group, a significant negative correlation was observed both between cervicovaginal washing prolactin concentrations and the lapsed times to delivery, and the gestational ages at delivery. The finding of a cervicovaginal washing prolactin value exceeding 50 ng/ml in the 12 days preceding preterm delivery had sensitivity, specificity, positive and negative predictive values of 65%, 95%, 86%, and 81%, respectively. CONCLUSIONS: A cervicovaginal washing prolactin value more than 50 ng/ml precedes preterm delivery within 12 days at > 29 weeks. The easy application, the good feasibility, the success in identifying pregnancies at risk for preterm labor, and the cost effectiveness suggests cervicovaginal washing prolactin assay as a biochemical marker for preterm delivery.

Adult↗
PubMed2000

Endometrial prolactin in hyperprolactinemic women.

OBJECTIVE: To observe the behavior of endometrial prolactin in hyper- and normoprolactinemic women. METHOD: Forty women were selected due to alterations in menstrual cycle and/or galactorrhea and/or sterility. Patients were divided into two groups: Group A, 19 hyperprolactinemic women; and Group B, 21 normoprolactinemic women. Their mean age was 28.3 years. Laboratory assessments were carried out in the initial follicular phase (days 3-9), initial luteal phase (days 15-21), and late luteal phase (days 22-29) in menstruating women (samples 1, 2 and 3, respectively). In the non-menstruating women, samples were collected on days 1, 14 and 21 after the initial appointment (samples 1, 2 and 3, respectively). LH, FSH, prolactin and estradiol were measured in sample 1, while prolactin and progesterone were measured in samples 2 and 3. All women were submitted to two biopsies of the endometrium for observing the menstrual cycle, dating, and immunohistochemical detection of endometrial prolactin. Biopsies were obtained simultaneously to samples 2 and 3. To compare the two groups, Student's t-tests or Mann-Whitney statistics were performed. RESULT: Results showed that the mean percentage of endometrial prolactin were higher in the late luteal phase compared to the initial one in hyper- and normoprolactinemic women. CONCLUSION: The data allowed us to conclude that serum prolactin is not correlated to endometrial prolactin, and that the synthesis of the latter is directly correlated to the differentiation of stromal cells, that is induced by progesterone in a decidualized endometrium.

Adult↗