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British Medical Journal (Clinical... Jan 1985
Review
Topics: Bromocriptine; Female; Humans; Male; Pituitary Neoplasms; Prolactin
PubMed: 3917745
DOI: 10.1136/bmj.290.6463.182 -
Neuroendocrinology 2021Motherhood entails increased motivation for pups, which become strong reinforcers and guide maternal behaviours. This depends on steroids and lactogens acting on the...
Motherhood entails increased motivation for pups, which become strong reinforcers and guide maternal behaviours. This depends on steroids and lactogens acting on the brain of females during pregnancy and postpartum. Since virgin female mice exposed to pups are nearly spontaneously maternal, the specific roles of endocrine and pup-derived signals in the induction of maternal motivation remain unclear. This work investigates maternal motivation in dams and virgin female mice, using a novel variant of the pup retrieval paradigm, the motivated pup retrieval test. We also analyse the role of prolactin (PRL) and of stimuli derived from a litter of pups and its mother, in the acquisition of maternal motivation. Experimental design included female mice in 3 conditions: lactating dams, comothers (virgins housed and sharing pup care with dams) and pup-naïve virgins. Females underwent 3 motivated-pup-retrieval trials, with pups displaced behind a 10-cm-high wire-mesh barrier. Dams retrieved with significantly lower latencies than comothers or virgins, indicating that full maternal motivation appears only after pregnancy. Although initially comothers and virgins showed no retrieval, comothers significantly improved throughout the experiment, suggesting an induced sensitization process. Lengthening exposure of comothers to the dyad pups-dam (from 2 to 5 days at the beginning of testing) had no strong effects on maternal sensitization. PRL responsiveness was analysed in these animals using immunohistochemical detection of phosphorylated signal transducer and activator of transcription 5 (pSTAT5, PRL-derived signalling marker). As expected, dams showed significantly higher pSTAT5 expression in most of the analysed nuclei. Moreover, comothers displayed significantly higher PRL responsiveness than pup-naïve virgins in the medial preoptic nucleus, even if they display similar circulating PRL levels, which are significantly lower than those of dams. Given the instrumental role of this nucleus in the relay and integration of pup-derived stimuli to facilitate proactive maternal responses, this increase in PRL responsiveness likely reflects the mechanism underlying the maternal sensitization process reported in this work. Since the analyses of maternal motivation and PRL signalling in the brain were performed in the same animals, we were able to explore correlation between both set of data. The results shed light on the neuroendocrine mechanisms underlying maternal motivation and other aspects of maternal behaviour.
Topics: Animals; Animals, Newborn; Behavior, Animal; Female; Maternal Behavior; Mice; Motivation; Prolactin
PubMed: 32645699
DOI: 10.1159/000510038 -
Journal of Molecular Endocrinology Jan 2021Pituitary cells have been reported to show spontaneous calcium oscillations and dynamic transcription cycles. To study both processes in the same living cell in real...
Pituitary cells have been reported to show spontaneous calcium oscillations and dynamic transcription cycles. To study both processes in the same living cell in real time, we used rat pituitary GH3 cells stably expressing human prolactin-luciferase or prolactin-EGFP reporter gene constructs loaded with a fluorescent calcium indicator and measured activity using single-cell time-lapse microscopy. We observed heterogeneity between clonal cells in the calcium activity and prolactin transcription in unstimulated conditions. There was a significant correlation between cells displaying spontaneous calcium spikes and cells showing spontaneous bursts in prolactin expression. Notably, cells showing no basal calcium activity showed low prolactin expression but elicited a significantly greater transcriptional response to BayK8644 compared to cells showing basal calcium activity. This suggested the presence of two subsets of cells within the population at any one time. Fluorescence-activated cell sorting was used to sort cells into two populations based on the expression level of prolactin-EGFP however, the bimodal pattern of expression was restored within 26 h. Chromatin immunoprecipitation showed that these sorted populations were distinct due to the extent of histone acetylation. We suggest that maintenance of a heterogeneous bimodal population is a fundamental characteristic of this cell type and that calcium activation and histone acetylation, at least in part, drive prolactin transcriptional competence.
Topics: Acetylation; Animals; Calcium; Cell Line; Chromatin Assembly and Disassembly; Genetic Heterogeneity; Histones; Prolactin; Rats; Single-Cell Analysis; Transcription, Genetic
PubMed: 33112804
DOI: 10.1530/JME-20-0223 -
Frontiers in Endocrinology 2021Prolactin (PRL) is a hormone produced by the pituitary gland and multiple non-pituitary sites, vital in several physiological processes such as lactation, pregnancy,... (Review)
Review
Prolactin (PRL) is a hormone produced by the pituitary gland and multiple non-pituitary sites, vital in several physiological processes such as lactation, pregnancy, cell growth, and differentiation. However, PRL is nowadays known to have a strong implication in oncogenic processes, making it essential to delve into the mechanisms governing these actions. PRL and its receptor (PRLR) activate a series of effects such as survival, cellular proliferation, migration, invasion, metastasis, and resistance to treatment, being highly relevant in developing certain types of cancer. Because women produce high levels of PRL, its influence in gynecological cancers is herein reviewed. It is interesting that, other than the 23 kDa PRL, whose mechanism of action is endocrine, other variants of PRL have been observed to be produced by tumoral tissue, acting in a paracrine/autocrine manner. Because many components, including PRL, surround the microenvironment, it is interesting to understand the hormone's modulation in cancer cells. This work aims to review the most important findings regarding the PRL/PRLR axis in cervical, ovarian, and endometrial cancers and its molecular mechanisms to support carcinogenesis.
Topics: Cell Transformation, Neoplastic; Female; Genital Neoplasms, Female; Humans; Prolactin; Receptors, Prolactin; Signal Transduction; Tumor Microenvironment
PubMed: 34745013
DOI: 10.3389/fendo.2021.747810 -
PloS One 2011The anterior pituitary is under a constant cell turnover modulated by gonadal steroids. In the rat, an increase in the rate of apoptosis occurs at proestrus whereas a...
The anterior pituitary is under a constant cell turnover modulated by gonadal steroids. In the rat, an increase in the rate of apoptosis occurs at proestrus whereas a peak of proliferation takes place at estrus. At proestrus, concomitant with the maximum rate of apoptosis, a peak in circulating levels of prolactin is observed. Prolactin can be cleaved to different N-terminal fragments, vasoinhibins, which are proapoptotic and antiproliferative factors for endothelial cells. It was reported that a 16 kDa vasoinhibin is produced in the rat anterior pituitary by cathepsin D. In the present study we investigated the anterior pituitary production of N-terminal prolactin-derived fragments along the estrous cycle and the involvement of estrogens in this process. In addition, we studied the effects of a recombinant vasoinhibin, 16 kDa prolactin, on anterior pituitary apoptosis and proliferation. We observed by Western Blot that N-terminal prolactin-derived fragments production in the anterior pituitary was higher at proestrus with respect to diestrus and that the content and release of these prolactin forms from anterior pituitary cells in culture were increased by estradiol. A recombinant preparation of 16 kDa prolactin induced apoptosis (determined by TUNEL assay and flow cytometry) of cultured anterior pituitary cells and lactotropes from ovariectomized rats only in the presence of estradiol, as previously reported for other proapoptotic factors in the anterior pituitary. In addition, 16 kDa prolactin decreased forskolin-induced proliferation (evaluated by BrdU incorporation) of rat total anterior pituitary cells and lactotropes in culture and decreased the proportion of cells in S-phase of the cell cycle (determined by flow cytometry). In conclusion, our study indicates that the anterior pituitary production of 16 kDa prolactin is variable along the estrous cycle and increased by estrogens. The antiproliferative and estradiol-dependent proapoptotic actions of this vasoinhibin may be involved in the control of anterior pituitary cell renewal.
Topics: Animals; Apoptosis; Cells, Cultured; Estradiol; Estrus; Female; Molecular Weight; Peptide Fragments; Pituitary Gland, Anterior; Prolactin; Rats; Rats, Wistar
PubMed: 21760910
DOI: 10.1371/journal.pone.0021806 -
American Journal of Physiology.... Jun 2022Prolactin (PRL) cells within the (RPD) of euryhaline and eurythermal Mozambique tilapia, , rapidly respond to a hyposmotic stimulus by releasing two distinct PRL...
Prolactin (PRL) cells within the (RPD) of euryhaline and eurythermal Mozambique tilapia, , rapidly respond to a hyposmotic stimulus by releasing two distinct PRL isoforms, PRL and PRL. Here, we describe how environmentally relevant temperature changes affected mRNA levels of and and the release of immunoreactive prolactins from RPDs and dispersed PRL cells. When applied under isosmotic conditions (330 mosmol/kgHO), a 6°C rise in temperature stimulated the release of PRL and PRL from both RPDs and dispersed PRL cells under perifusion. When exposed to this same change in temperature, ∼50% of dispersed PRL cells gradually increased in volume by ∼8%, a response partially inhibited by the water channel blocker, mercuric chloride. Following their response to increased temperature, PRL cells remained responsive to a hyposmotic stimulus (280 mosmol/kgHO). The mRNA expression of , a Ca-channel involved in hyposmotically induced PRL release, was elevated in response to a rise in temperature in dispersed PRL cells and RPDs at 6 and 24 h, respectively; and mRNAs were unaffected. Our findings indicate that thermosensitive PRL release is mediated, at least partially, through a cell-volume-dependent pathway similar to how osmoreceptive PRL release is achieved.
Topics: Animals; Cell Size; Pituitary Gland; Prolactin; RNA, Messenger; Tilapia; Water
PubMed: 35438003
DOI: 10.1152/ajpregu.00027.2022 -
Journal of Human Lactation : Official... Feb 2020Maternal milk production requires the neuropeptide oxytocin. Individual variation in oxytocin function is a compelling target for understanding low milk production, a...
BACKGROUND
Maternal milk production requires the neuropeptide oxytocin. Individual variation in oxytocin function is a compelling target for understanding low milk production, a leading cause of breastfeeding attrition. Complicating the understanding of oxytocin pathways is that vasopressin may interact with oxytocin receptors, yet little is known about the role of vasopressin in lactation.
RESEARCH AIMS
The aims of this study were (1) to describe maternal plasma oxytocin, vasopressin, and prolactin patterns during breastfeeding following low-risk spontaneous labor and birth in healthy first-time mothers and (2) to relate hormone patterns to maternal characteristics and breastfeeding measures.
METHODS
Eligible women were recruited before hospital discharge. Forty-six participants enrolled and 35 attended the study visit. Participants kept a journal of breastfeeding frequency, symptoms of lactogenesis, and infant weight. Plasma samples were obtained at breastfeeding onset on Day 4-5 postpartum, and repeated after 20 min. Hormones were measured with immunoassays. Infant weight change, milk transfer, and onset of lactogenesis were also measured.
RESULTS
Baseline oxytocin and vasopressin were inversely related to one another. Oxytocin and prolactin increased significantly across the 20-min sampling period while vasopressin decreased. Higher oxytocin was associated with higher maternal age, lower BMI, shorter active labor, physiologic labor progression, and less weight loss in the newborn. Higher vasopressin correlated with younger maternal age, higher BMI, and greater newborn weight loss.
CONCLUSIONS
Oxytocin and vasopressin have contrasting relationships with maternal clinical characteristics and newborn weight gain in early breastfeeding infants. Further study is needed to understand how oxytocin and vasopressin influence lactation outcomes.
Topics: Adult; Body-Weight Trajectory; Breast Feeding; Female; Humans; Infant, Newborn; Oregon; Oxytocin; Prolactin; Vasopressins
PubMed: 31033381
DOI: 10.1177/0890334419838225 -
The Journal of Biological Chemistry Feb 1986Rat prolactin exhibits microheterogeneity when examined in electrophoretic systems, running as three isoforms having the same molecular weight but different net charges... (Comparative Study)
Comparative Study
Rat prolactin exhibits microheterogeneity when examined in electrophoretic systems, running as three isoforms having the same molecular weight but different net charges (prolactins 1, 2, and 3 with isoform 3 being the most acidic). As there is precedent for the phosphorylation of a pituitary hormone and phosphorylation is a common cause of microheterogeneity, we examined the possibility that rat prolactin existed in differentially phosphorylated forms. The investigation included examinations of rat prolactin phosphorylation both in vitro and in vivo. For the in vitro studies, purified rat prolactin was incubated with [gamma-32P]ATP and low levels of each of five purified protein kinases. Phosphorylated rat prolactin was identified by autoradiography of silver-stained one- and two-dimensional gels. For the in vivo studies, rat anterior pituitary cells in primary culture were incubated in the presence of H3 32PO4 for 2 or 12 h, after which time the proteins were extracted from the cells, cold acetone-precipitated, or immunoprecipitated and run on two-dimensional gels. We report the in vitro phosphorylation of rat prolactin by cAMP-dependent protein kinase, casein kinase I, protease-activated kinase I, and the calcium/phospholipid-dependent kinase, that phosphorylation with these kinases results in phosphate incorporation only into isoforms 2 and 3, and the phosphorylation of prolactin in rat pituitary cells in primary culture.
Topics: Animals; Casein Kinases; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Peptide Hydrolases; Peptidyl-Dipeptidase A; Phosphorylation; Pituitary Gland, Anterior; Prolactin; Protein Kinase C; Protein Kinases; Rats
PubMed: 3003080
DOI: No ID Found -
Biochemia Medica Jun 2019Macroprolactinaemia is a well-known analytical problem in diagnostics of hyperprolactinaemia usually detected with polyethylene glycol (PEG) precipitation method. Since...
INTRODUCTION
Macroprolactinaemia is a well-known analytical problem in diagnostics of hyperprolactinaemia usually detected with polyethylene glycol (PEG) precipitation method. Since there is no harmonization in macroprolactin detection and reporting results, this study proposes and evaluates the usefulness of in-house developed algorithm. The aims were to determine the most suitable way of reporting results after PEG treatment and the possibilities of rationalizing the precipitation procedure.
MATERIALS AND METHODS
This is a retrospective study based on extracted data for 1136 patients. Prolactin concentrations were measured before and after PEG precipitation on Roche cobas e601. Macroprolactinaemia was defined by percentage recovery and post-PEG prolactin concentrations.
RESULTS
Prevalence of macroprolactinaemia using recovery criteria of ≤ 40%, ≤ 60%, and post-PEG prolactin concentrations was 3.3%, 8.8% and 7.8%, respectively. Raising the cut-off value from the upper limit of the manufacturer's reference interval to 32.9 µg/L does not drastically change detected macroprolactinaemia with recovery criteria. Post-PEG prolactin concentrations showed more than half of the patients with macroprolactinaemia would be overlooked. Regardless of the criteria, a cut-off of 47.0 µg/L would miss most of the macroprolactinaemic patients. Repeated recovery measurements of follow-up patients showed there is a significant difference with mean absolute bias of 9%.
CONCLUSIONS
Post-PEG prolactin concentration with corresponding reference interval is the most suitable way of reporting results. All samples with prolactin concentration above the upper limit of the manufacturer's reference interval should be submitted to PEG precipitation. Follow-up period could be prolonged since the difference between the recoveries of repeated measurements is not clinically significant.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Clinical Laboratory Techniques; Female; Humans; Male; Middle Aged; Prolactin; Retrospective Studies; Young Adult
PubMed: 31223260
DOI: 10.11613/BM.2019.020706 -
Fertility and Sterility Oct 1997To investigate intraovarian prolactin and prolactin-receptor gene expression and to assess local prolactin synthesis with emphasis on possible differences between... (Comparative Study)
Comparative Study
OBJECTIVE
To investigate intraovarian prolactin and prolactin-receptor gene expression and to assess local prolactin synthesis with emphasis on possible differences between premenopausal and postmenopausal status.
DESIGN
The RNA extracted from human premenopausal and postmenopausal tissues was subjected to reverse transcription and polymerase chain reaction by using prolactin-specific intron- and exon-spanning primers. Prolactin-receptor expression was investigated accordingly. The amplified complementary DNA fragments were analyzed by gel electrophoresis and restriction enzyme mapping. Local prolactin hormone synthesis was verified by a time-resolved immunofluorometric assay based on our monoclonal antibodies.
RESULT(S)
Prolactin and prolactin-receptor gene expression was observed in all analyzed human ovaries (n = 18). Several other human tissue specimens, such as lung and kidney, served as negative control tissues. Significantly elevated concentrations of prolactin were detected in cytosolic extracts of premenopausal (n = 6; mean +/- SD; 20.6 +/- 3.3 ng/g tissue wet weight) versus postmenopausal (n = 6; 3.6 +/- 3.0 ng/g tissue wet weight) ovaries.
CONCLUSION(S)
The human ovary not only serves as a target for endocrine prolactin action but also as a site of local prolactin hormone production. In agreement with previous reports on extrapituitary sources of prolactin, we consider prolactin as a hormone as well as an autocrine or paracrine growth or regulatory factor. Significantly increased concentrations of prolactin in premenopausal ovarian tissue verifies its role in human reproduction.
Topics: Adult; Cytosol; Female; Gene Expression; Humans; Middle Aged; Osmolar Concentration; Ovary; Postmenopause; Premenopause; Prolactin; Receptors, Prolactin
PubMed: 9341613
DOI: 10.1016/s0015-0282(97)00320-8