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Hormones and Behavior Aug 2022Prolactin, a hormone involved in vertebrate parental care, is hypothesized to inhibit reproductive hypothalamic-pituitary-gonadal (HPG) axis activity during parenting,...
Prolactin, a hormone involved in vertebrate parental care, is hypothesized to inhibit reproductive hypothalamic-pituitary-gonadal (HPG) axis activity during parenting, thus maintaining investment in the current brood as opposed to new reproductive efforts. While prolactin underlies many parental behaviors in birds, its effects on other reproductive behaviors, such as courtship, remain unstudied. How prolactin affects neuropeptide and hormone receptor expression across the avian HPG axis also remains unknown. To address these questions, we administered ovine prolactin (oPRL) or a vehicle control to both sexes in experienced pairs of the biparental rock dove (Columba livia), after nest removal at the end of incubation. We found that oPRL promoted parental responses to novel chicks and stimulated crop growth compared to controls, consistent with other studies. However, we found that neither courtship behaviors, copulation rates nor pair maintenance differed with oPRL treatment. Across the HPG, we found oPRL had little effect on gene expression in hypothalamic nuclei, but increased expression of FSHB and hypothalamic hormone receptor genes in the pituitary. In the gonads, oPRL increased testes size and gonadotropin receptor expression, but did not affect ovarian state or small white follicle gene expression. However, the oviducts of oPRL-treated females were smaller and had lower estrogen receptor expression compared with controls. Our results highlight that some species, especially those that show multiple brooding, may continue to express mating behavior despite elevated prolactin. Thus, mechanisms may exist for prolactin to promote investment in parental care without concurrent inhibition of reproductive function or HPG axis activity.
Topics: Animals; Columbidae; Female; Gene Expression; Gonads; Male; Prolactin; Reproduction; Sheep
PubMed: 35785711
DOI: 10.1016/j.yhbeh.2022.105217 -
Clinical Chemistry and Laboratory... Oct 2017Hyperprolactinemia diagnosis and treatment is often compromised by the presence of biologically inactive and clinically irrelevant higher-molecular-weight complexes of...
Serum prolactin revisited: parametric reference intervals and cross platform evaluation of polyethylene glycol precipitation-based methods for discrimination between hyperprolactinemia and macroprolactinemia.
BACKGROUND
Hyperprolactinemia diagnosis and treatment is often compromised by the presence of biologically inactive and clinically irrelevant higher-molecular-weight complexes of prolactin, macroprolactin. The objective of this study was to evaluate the performance of two macroprolactin screening regimes across commonly used automated immunoassay platforms.
METHODS
Parametric total and monomeric gender-specific reference intervals were determined for six immunoassay methods using female (n=96) and male sera (n=127) from healthy donors. The reference intervals were validated using 27 hyperprolactinemic and macroprolactinemic sera, whose presence of monomeric and macroforms of prolactin were determined using gel filtration chromatography (GFC).
RESULTS
Normative data for six prolactin assays included the range of values (2.5th-97.5th percentiles). Validation sera (hyperprolactinemic and macroprolactinemic; n=27) showed higher discordant classification [mean=2.8; 95% confidence interval (CI) 1.2-4.4] for the monomer reference interval method compared to the post-polyethylene glycol (PEG) recovery cutoff method (mean=1.8; 95% CI 0.8-2.8). The two monomer/macroprolactin discrimination methods did not differ significantly (p=0.089). Among macroprolactinemic sera evaluated by both discrimination methods, the Cobas and Architect/Kryptor prolactin assays showed the lowest and the highest number of misclassifications, respectively.
CONCLUSIONS
Current automated immunoassays for prolactin testing require macroprolactin screening methods based on PEG precipitation in order to discriminate truly from falsely elevated serum prolactin. While the recovery cutoff and monomeric reference interval macroprolactin screening methods demonstrate similar discriminative ability, the latter method also provides the clinician with an easy interpretable monomeric prolactin concentration along with a monomeric reference interval.
Topics: Adolescent; Adult; Aged; Case-Control Studies; Chemical Precipitation; Confidence Intervals; Diagnosis, Differential; Female; Humans; Hyperprolactinemia; Immunoassay; Male; Middle Aged; Polyethylene Glycols; Prolactin; Prolactinoma; Reagent Kits, Diagnostic; Reference Values; Young Adult
PubMed: 28236625
DOI: 10.1515/cclm-2016-0902 -
Journal of Clinical Laboratory Analysis Nov 2017Proteolytic cleavage through proteases affects peptide hormone levels, which is of particular significance when the time interval between sampling and analysis is...
The effect of different protease inhibitors on stability of parathyroid hormone, insulin, and prolactin levels under different lag times and storage conditions until analysis.
INTRODUCTION
Proteolytic cleavage through proteases affects peptide hormone levels, which is of particular significance when the time interval between sampling and analysis is prolonged. We evaluated the stability of parathyroid hormone, insulin, and prolactin molecules (i) with different protease inhibitors such as K EDTA, aprotinin, and protease inhibitor cocktail (PIC), (ii) with different lag times (6-72 hours), and (iii) under different storage temperatures (4°C vs room temperature [RT]) until analysis.
MATERIALS AND METHODS
Blood samples were collected into 2 sets of 5 Vacutainer tubes (Becton Dickinson) from 10 healthy adults. Tubes 1 and 2 were plain gel separator tubes. Tubes 3, 4, and 5 contained PIC (1%), aprotinin (500 KIU/mL), and K EDTA, respectively. After centrifugation at 1300 g for 10 minutes, PIC added to tube 2 of each set. Samples were analyzed and then one set was stored at 4°C, whereas the other at RT until analysis at 6, 24, 48, and 72 hours. Hormone levels were determined with electrochemiluminescence immunoassay (ModularE170; Roche Diagnostics). The results were compared with desirable bias limits (DBL) from Westgard QC database.
RESULTS
Insulin at RT decreases exceeding the DBL starting from 24 hours and K EDTA preserved insulin. PTH exceeded the DBL at RT for 48 hours or longer and PIC addition after centrifugation inhibited its degradation. Prolactin remained stable in all tested conditions. All parameters in the plain gel separator tubes remained within DBL when stored at 4°C until 72 hours.
CONCLUSIONS
Different proteases may degrade peptide hormones and measures should be taken to counteract these effects especially if there is a delay before analysis.
Topics: Adult; Blood Specimen Collection; Female; Humans; Immunoassay; Insulin; Male; Parathyroid Hormone; Prolactin; Protease Inhibitors; Protein Stability; Young Adult
PubMed: 28133791
DOI: 10.1002/jcla.22144 -
Communications Biology Jan 2021In many species, ejaculation is followed by a state of decreased sexual activity, the post-ejaculatory refractory period. Several lines of evidence have suggested...
In many species, ejaculation is followed by a state of decreased sexual activity, the post-ejaculatory refractory period. Several lines of evidence have suggested prolactin, a pituitary hormone released around the time of ejaculation in humans and other animals, to be a decisive player in the establishment of the refractory period. However, data supporting this hypothesis is controversial. We took advantage of two different strains of house mouse, a wild derived and a classical laboratory strain that differ substantially in their sexual performance, to investigate prolactin's involvement in sexual activity and the refractory period. First, we show that there is prolactin release during sexual behavior in male mice. Second, using a pharmacological approach, we show that acute manipulations of prolactin levels, either mimicking the natural release during sexual behavior or inhibiting its occurrence, do not affect sexual activity or shorten the refractory period, respectively. Therefore, we show compelling evidence refuting the idea that prolactin released during copulation is involved in the establishment of the refractory period, a long-standing hypothesis in the field of behavioral endocrinology.
Topics: Animals; Female; Male; Mice, Inbred C57BL; Prolactin; Sexual Behavior, Animal; Mice
PubMed: 33398068
DOI: 10.1038/s42003-020-01570-4 -
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 -
Journal of Molecular Biology Aug 2005We report the solution structure of human prolactin determined by NMR spectroscopy. Our result is a significant improvement over a previous structure in terms of number... (Comparative Study)
Comparative Study
We report the solution structure of human prolactin determined by NMR spectroscopy. Our result is a significant improvement over a previous structure in terms of number and distribution of distance restraints, regularity of secondary structure, and potential energy. More significantly, the structure is sufficiently different that it leads to different conclusions regarding the mechanism of receptor activation and initiation of signal transduction. Here, we compare the structure of unbound prolactin to structures of both the homologue ovine placental lactogen and growth hormone. The structures of unbound and receptor bound prolactin/placental lactogen are similar and no noteworthy structural changes occur upon receptor binding. The observation of enhanced binding at the second receptor site when the first site is occupied has been widely interpreted to indicate conformational change induced by binding the first receptor. However, our results indicate that this enhanced binding at the second site could be due to receptor-receptor interactions or some other free energy sources rather than conformational change in the hormone. Titration of human prolactin with the extracellular domain of the human prolactin receptor was followed by NMR, gel filtration and electrophoresis. Both binary and ternary hormone-receptor complexes are clearly detectable by gel filtration and electrophoresis. The binary complex is not observable by NMR, possibly due to a dynamic equilibrium in intermediate exchange within the complex. The ternary complex of one hormone molecule bound to two receptor molecules is on the contrary readily detectable by NMR. This is in stark contrast to the widely held view that the ternary prolactin-receptor complex is only transiently formed. Thus, our results lead to improved understanding of the prolactin-prolactin receptor interaction.
Topics: Amino Acid Sequence; Animals; Binding Sites; Human Growth Hormone; Humans; In Vitro Techniques; Models, Molecular; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; Placental Lactogen; Prolactin; Protein Conformation; Receptors, Prolactin; Recombinant Proteins; Sequence Homology, Amino Acid; Sheep; Solutions
PubMed: 16045928
DOI: 10.1016/j.jmb.2005.06.042 -
General and Comparative Endocrinology Aug 2021Our understanding of the hormonal mechanisms underlying parental care mainly stems from research on species with uniparental care. Far less is known about the...
Our understanding of the hormonal mechanisms underlying parental care mainly stems from research on species with uniparental care. Far less is known about the physiological changes underlying motherhood and fatherhood in biparental caring species. Here, using two biparental caring cichlid species (Neolamprologus caudopunctatus and Neolamprologus pulcher), we explored the relative gene-expression levels of two genes implicated in the control of parental care, galanin (gal) and prolactin (prl). We investigated whole brain gene expression levels in both, male and female caring parents, as well as in non-caring individuals of both species. Caring males had higher prl and gal mRNA levels compared to caring females in both fish species. Expression of gal was highest when young were mobile and the need for parental defense was greatest and gal was lowest during the more stationary egg tending phase in N. caudopunctatus. The onset of parenthood was associated with lower expression of prl and higher expression of gal in N. pulcher, but this pattern was not observed in N. caudopunctatus. Our study demonstrates that gal gene expression is correlated with changes in parental care in two biparental cichlid species and extends both knowledge and taxonomic coverage of the possible neurogenetic mechanisms underlying parental care.
Topics: Animals; Cichlids; Female; Galanin; Lakes; Male; Prolactin; Tanzania
PubMed: 33862047
DOI: 10.1016/j.ygcen.2021.113785 -
General and Comparative Endocrinology May 2014Prolactin acts on target cells in the central nervous system (CNS) to stimulate behavioral changes associated with parental care in birds, but the signaling mechanisms...
Prolactin acts on target cells in the central nervous system (CNS) to stimulate behavioral changes associated with parental care in birds, but the signaling mechanisms that mediate these actions have not been characterized. In mammals, the Janus Kinase 2-Signal Transducer and Activator of Transcription 5 (JAK2-STAT5) signaling pathway mediates many of the actions of prolactin. To assess the importance of this pathway in prolactin-sensitive target cells in the avian brain, we measured changes in activated (phosphorylated) STAT5 (pSTAT5) in the forebrain of female ring doves sampled as plasma prolactin levels change during the breeding cycle and in prolactin-treated, non-breeding females. The anatomical distribution of cells exhibiting pSTAT5 immunoreactivity in dove brain closely paralleled the distribution of prolactin receptors in this species. The density of pSTAT5 immunoreactive (pSTAT5-ir) cells was highest in the preoptic area, the suprachiasmatic, paraventricular, and ventromedial hypothalamic nuclei, the lateral and tuberal hypothalamic regions, the lateral bed nucleus of the stria terminalis, and the lateral septum. Mean pSTAT5-ir cell densities in these eight brain areas were several fold higher in breeding females during late incubation/early post-hatching when plasma prolactin levels have been observed to peak than in non-breeding females or breeding females sampled at earlier stages when prolactin titers have been reported to be lower. Similar differences were observed between prolactin-treated and vehicle-treated females in all three of the forebrain regions that were compared. We conclude that JAK2-STAT5 signaling is strongly activated in response to prolactin stimulation in the ring dove brain and could potentially mediate some of the centrally-mediated behavioral effects of this hormone.
Topics: Animals; Brain; Breeding; Cell Count; Columbidae; Female; Male; Phosphorylation; Prolactin; Receptors, Prolactin; Reproduction; STAT5 Transcription Factor; Sheep; Signal Transduction
PubMed: 24530808
DOI: 10.1016/j.ygcen.2014.02.006 -
The American Journal of Managed Care Oct 2001The etiologic enigma of systemic lupus erythematosus (SLE) has so far precluded a fully integrated approach to understanding and managing the disease. As new findings... (Review)
Review
The etiologic enigma of systemic lupus erythematosus (SLE) has so far precluded a fully integrated approach to understanding and managing the disease. As new findings continue to uncover relationships between the endocrine system and the besieged immune system in lupus patients, however, researchers have an opportunity to rethink the direction of their investigative efforts. A successful approach to development of long-awaited new treatments may well include modulation of specific hormones. The peptide hormone prolactin may be associated with SLE disease activity. The dopamine agonist bromocriptine, which inhibits pituitary secretion of prolactin, has been shown in a variety of small animal and human trials to reduce disease activity in SLE. Continued research may show that it can be an attractive alternative or adjacent therapy in cases where hydroxychloroquine is contraindicated.
Topics: Animals; Bromocriptine; Dopamine Agonists; Estrogens; Hormones; Humans; Lupus Erythematosus, Systemic; Prolactin; Testosterone
PubMed: 11680780
DOI: No ID Found -
Hormones and Behavior Oct 2009Prolactin has been implicated in promoting paternal care behaviors but little evidence of causality has been found to date except for birds and fish. This study was...
Prolactin has been implicated in promoting paternal care behaviors but little evidence of causality has been found to date except for birds and fish. This study was designed to examine the possible causal relationships between prolactin and male parenting behaviors, reproductive hormones, and physical changes in cooperatively breeding common marmosets, Callithrix jacchus. Fifteen parentally experienced fathers were studied over three consecutive infant care periods during two weeks prior and three weeks following their mates' parturition under three-treatment conditions: normal control pregnancy, decreased prolactin and elevated prolactin. The treatments significantly altered the serum prolactin levels in the fathers. Using three methods of determining a father's level of parental care: infant carrying, family effort and responsiveness to infant stimulus tests, we found that only the male response to infant stimuli was altered by the hormone treatments. Lowering prolactin significantly reduced male responsiveness to infant stimuli but elevating prolactin showed the same effect. Hormonal sampling indicated that testosterone levels showed an inverse relationship to prolactin levels during a normal peripartum period and prolactin treatment reduced this relationship. Prepartum estradiol levels were significantly elevated during the lowered prolactin treatment and estradiol was significantly lowered postpartum with the elevated prolactin treatment. Father's weight decreased significantly by the third week of infant care during the normal treatment. Males in the elevated prolactin treatment lost little or no weight from prepartum while in the lowered prolactin treatment showed the most weight loss. The present findings did not distinguish a direct causal relationship of prolactin on behavior in experienced fathers but did find an interaction with other hormones and weight gain.
Topics: Analysis of Variance; Animals; Behavior, Animal; Body Weight; Callithrix; Estradiol; Fathers; Male; Paternal Behavior; Prolactin; Random Allocation; Testosterone; Time Factors; Weight Loss
PubMed: 19664636
DOI: 10.1016/j.yhbeh.2009.07.012