Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PROLACTIN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,495 records · Page 83Linked to original sources
PubMed1983

In vivo lactogenic effects of anti prolactin receptor antibodies in pseudopregnant rabbits.

Antibodies generated against partially purified prolactin receptors from rabbit mammary gland membranes were tested for their effects on prolactin binding to receptors and for their in vivo biological potencies. These antibodies are able to inhibit prolactin binding to crude rabbit mammary gland membranes. When administered intravenously or intramuscularly to pseudopregnant rabbits, they induce respectively an accumulation of beta-casein or an enhancement of beta-casein synthesis and mRNA concentration in the mammary gland. Moreover the stimulatory effect of these anti-prolactin receptor antibodies on casein synthesis is totally abolished by a simultaneous treatment with progesterone, which is a potent in vivo inhibitor of prolactin action. These results better establish the prolactin-like activities of these antibodies previously observed in vitro and give strong support to the hypothesis that prolactin molecule is not required beyond the initial binding to its receptor to induce hormonal effects.

Animals↗
PubMed1984

Prolactin binding in the developing rat fetal liver.

The binding of prolactin by fetal rat liver cell membrane fractions from 17 to 21 days gestation was studied. Particulate liver membranes were prepared in Dulbecco's Phosphate Buffered Saline (PBS) by ultracentrifugation and incubated at 22 degrees C for 16 hours with [125I] iodo-human growth hormone (hGH). Non-specific binding was assessed by parallel incubations in the presence of a 2000-fold excess ovine prolactin. Specific prolactin binding sites were detected only at 21 days gestation (2932 +/- 401 cpm/mg protein) in freshly prepared membranes. On freezing at -20 degrees C for 24 to 48 hours, the membranes of 20 days gestation animals were able to specifically bind prolactin (1295 +/- 239 cpm/mg protein). Freezing led to a 45 +/- 7% increase (4270 +/- 701 cpm/mg protein) in prolactin binding at 21 days gestation. No hormonal binding was detected from 17 through 19 days gestation in either fresh or freeze-thawed membranes. Scatchard analysis revealed a high affinity binding site with a Ka of approximately 1.4 X 10(8)M-1 in both fresh and freeze-thawed membrane preparations. The data show that 1) prolactin receptors appear in liver only during late fetal life and that 2) freezing of membranes may unmask binding sites that are initially unavailable to specifically bind prolactin.

Animals↗
PubMed2005

Solution structure of human prolactin.

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.

Amino Acid Sequence↗
PubMed1998

Phosphorylation of bovine prolactin eliminates luteotropic activity in the rat.

Phosphorylated and nonphosphorylated prolactins were isolated from bovine pituitaries and their luteotropic activity determined in female rats. Three groups of rats in day 1 of diestrus were treated i.p. twice daily for three days with 0.25 mg of either prolactin preparation or vehicle. Rats were sacrificed each day of treatment. Serum progesterone concentrations of the groups receiving vehicle or phosphorylated prolactin were similar and the vaginal cytology of these animals indicated that phosphorylated bovine prolactin (bPRL) treatment had not prolonged diestrus. Treatment with nonphosphorylated bPRL significantly increased serum progesterone concentration and the vaginal cytology indicated a diestrus prolonged for up to 4 days. Nonphosphorylated and phosphorylated bPRLs were cleared from the blood at similar rates after i.p. injection. In vitro receptor binding studies demonstrated that phosphorylated bPRL did not bind the ovarian prolactin receptor. Nonphosphorylated, but not phosphorylated, bPRL competed with radiolabeled bovine hormone for occupancy of rat ovarian prolactin receptors. These data are the first to test the activities of phosphorylated bPRL in vivo and indicate; 1) nonphosphorylated bPRL is luteotropic, 2) phosphorylated bPRL is neither luteotropic nor a prolactin receptor agonist or antagonist and 3) phosphorylated bPRL is not dephosphorylated in vivo rapidly enough to provide sufficient biologically-active bPRL to maintain luteal function.

Animals↗
PubMed1982

Prolactin receptors in interstitial cells of testes from rats at different stages of development.

The developmental pattern of prolactin receptors was examined in intact interstitial cells isolated from testes of 19-day old foetuses (F19), 1 to 45-day immature (N1 to N45) and adult animals. The prolactin binding activity in F19 interstitial cells is low, being 27% of that found in cells of the adult. There is an abrupt 60% increase in prolactin binding immediately after birth (N1), followed by a slow, but gradual, increase for the next 34 and adulthood which follows an increment in serum prolactin concentrations after day 24. Equilibrium analysis revealed that the receptors In interstitial cells from N1, N34 and adults have similar affinity (Kd = 2.7 to 3.3 x 10(-10)M) for prolactin. However, cells from adults contain twice as many prolactin receptors per cell as that of immature animals. This increase in prolactin receptors may play a role in the modulation of interstitial (Leydig) cell function during sexual maturation.

Animals↗
PubMed2000

Prolactin: structure, function, and regulation of secretion.

Prolactin is a protein hormone of the anterior pituitary gland that was originally named for its ability to promote lactation in response to the suckling stimulus of hungry young mammals. We now know that prolactin is not as simple as originally described. Indeed, chemically, prolactin appears in a multiplicity of posttranslational forms ranging from size variants to chemical modifications such as phosphorylation or glycosylation. It is not only synthesized in the pituitary gland, as originally described, but also within the central nervous system, the immune system, the uterus and its associated tissues of conception, and even the mammary gland itself. Moreover, its biological actions are not limited solely to reproduction because it has been shown to control a variety of behaviors and even play a role in homeostasis. Prolactin-releasing stimuli not only include the nursing stimulus, but light, audition, olfaction, and stress can serve a stimulatory role. Finally, although it is well known that dopamine of hypothalamic origin provides inhibitory control over the secretion of prolactin, other factors within the brain, pituitary gland, and peripheral organs have been shown to inhibit or stimulate prolactin secretion as well. It is the purpose of this review to provide a comprehensive survey of our current understanding of prolactin's function and its regulation and to expose some of the controversies still existing.

Alternative Splicing↗
PubMed1989

Autoradiographic identification of prolactin binding sites in rat median eminence.

Binding sites for prolactin were localized and quantified in the female rat brain by in vitro autoradiographic analysis with iodine-125-labeled ovine prolactin. Following incubation, labeled prolactin bound preferentially to the median eminence and choroid plexus of the lateral and third ventricles. The addition of excess unlabeled ovine prolactin blocked binding of the labeled hormone in the choroid plexus, and attenuated prolactin binding in the median eminence. These results provide evidence for median eminence. These results provide evidence for prolactin-specific recognition sites in the median eminence, a region intimately involved in the hypothalamic regulation of prolactin secretion.

Animals↗
PubMed2001

Effects of prolactin on hematopoiesis.

The presence of extra-pituitary prolactin and its cognitive receptors in the hematopoietic micro-environment raises the question of whether prolactin plays a role in lympho-hematopoiesis and under what conditions. Current studies suggest that endogenous prolactin does not play a significant role under normal steady-state conditions. Rather, prolactin has been implicated as a 'stress hormone', functioning to restore hematopoietic homeostasis under conditions of dysregulation. The stress response of prolactin as well as its complex relationship with other hormones and factors has resulted in conflicting reports in the literature regarding prolactin's role in lympho-hematopoiesis. A review of this literature is provided as well as discussion of conditions under which lymphohematopoietic activity of prolactin may be evident.

Animals↗
PubMed2001

Prolactin signalling to milk protein secretion but not to gene expression depends on the integrity of the Golgi region.

Prolactin added to the incubation medium of lactating mammary epithelial cells is transported from the basal to the apical region of cells through the Golgi region and concomitantly stimulates arachidonic acid release and protein milk secretion. We report that when PRL is added after disorganisation of the Golgi apparatus by brefeldin A treatment, prolactin signalling to expression of genes for milk proteins and prolactin endocytosis are not affected. However, prolactin transport to the apical region of cells (transcytosis), as well as prolactin-induced arachidonic acid release and subsequent stimulation of the secretion of caseins, which are located in a post-Golgi compartment, are inhibited. This inhibition was not a consequence of damage to the secretory machinery, as under the same conditions, protein secretion could be stimulated by the addition of arachidonic acid to the incubation medium. Thus, it is possible to discriminate between prolactin-induced actions that are dependent (signalling to milk protein secretion) or independent (signalling to milk gene expression) on the integrity of the Golgi apparatus. These results suggest that these two biological actions may be transduced via distinct intracellular pathways, and support the hypothesis that prolactin signals may be emitted at various cellular sites.

Animals↗
PubMed2004

A mutant receptor with enhanced dominant-negative activity for the blockade of human prolactin signalling.

An effective mechanism for interfering with prolactin signalling would provide a powerful tool for clarifying the importance of prolactin in breast cancer, as well as for investigating functions of prolactin in other tissues. Based on our previous identification of a dominant-negative mutation in the growth hormone receptor that causes familial short stature, we investigated the potential for using a similar truncated mutant of the prolactin receptor (PRLR1-242). Like the mutant growth hormone receptor, PRLR1-242 exerts an exceptionally powerful dominant-negative effect. A probable explanation for the strong dominant-negative activity of this class of mutation is that, lacking internalisation motifs, the truncated mutants accumulate at the cell surface and form non-functional heterodimers with wild-type receptors. In accordance with evidence for heterodimer formation between the two receptors, PRLR1-242 also blocks signalling by the growth hormone receptor. When expressed from an adenoviral vector, PRLR1-242 inhibits activation of STAT5 (signal transducer and activator of transcription 5) by prolactin in T47-D breast cancer cells, and blocks the ability of prolactin to induce proliferation in these cells. Thus PRLR1-242 provides an effective means of blocking the responsiveness of target tissues to human prolactin.

Adenoviridae↗
PubMed1982

Influence of glucocorticoids on mammary prolactin receptors in pregnant mice after ovariectomy.

Regulation of mammary prolactin receptors by steroid hormones was investigated in ovariectomized mid-pregnant mice. Ovariectomy increased the number of mammary prolactin receptors per cell with no effect or a slight decrease in dissociation constant (Kd). The simultaneous removal of adrenals prevented this increase in numbers. A single injection of glucocorticoid (corticosterone or cortisol) in ovariectomized-adrenalectomized mice restored the number of prolactin receptors in mammary glands to the same level as that in ovariectomized controls without changing the Kd. Aldosterone, deoxycorticosterone and oestradiol did not affect the number of mammary prolactin receptors after ovariectomy-adrenalectomy. Serum concentration of prolactin was not influenced by the hormone manipulation except with injections of oestradiol or cortisol and apparently did not correlate with the number of prolactin receptors. These results indicated that glucocorticoids are required for the increase in the number of mammary prolactin receptors induced by ovariectomy in mid-pregnant mice.

Adrenalectomy↗
PubMed1984

Differential effects of cryptorchidism and short photoperiod on testicular prolactin and LH/human chorionic gonadotrophin receptors in the golden hamster.

Gonadal atrophy induced by short photoperiods in male golden hamsters is accompanied by a decrease in the total content of testicular prolactin and LH/human chorionic gonadotrophin (LH/hCG) receptors and a concomitant rise in the concentrations of LH receptors. Atrophic testes are typically abdominal. In this study, we have compared the effects of experimentally induced cryptorchidism and the effects of a short photoperiod on testicular prolactin and LH/hCG receptors. Cryptorchidism produced the expected decrease in testicular weight and an increase in plasma FSH concentrations, without altering plasma concentrations of LH or prolactin and with a relatively small decrease in plasma testosterone. It also produced an increase in the concentration of prolactin and LH/hCG receptors without significant changes in their total content. Exposure to a short photoperiod decreased weights of testes and seminal vesicles and plasma levels of prolactin and testosterone, with no significant effects on plasma gonadotrophin levels. Short photoperiod also increased the concentration of LH/hCG receptors but, in contrast to the effects of cryptorchidism, it produced a precipitous decline in the total content of testicular receptors for both prolactin and LH/hCG. We conclude that changes in prolactin and hCG binding measured in membrane preparations from decapsulated testes of hamsters exposed to a short photoperiod cannot be explained by the abdominal position of the gonads, abnormalities of Sertoli cell function or changes in the relative proportion of Leydig cells in the atrophic testes.

Animals↗
PubMed2003

Specific window of prolactin inhibition in late gestation decreases mammary parenchymal tissue development in gilts.

Prolactin is required from d 70 to 110 of gestation for normal mammary development of gilts. The goal of the present study was to determine the effect of inhibiting prolactin with bromocriptine during specific time windows during the second half of gestation on mammary gland development in gilts. Crossbred primigravid gilts were assigned as controls (n = 12) or received 10 mg of bromocriptine orally three times daily from d 50 to 69 (BR50, n = 12), d 70 to 89 (BR70, n = 12), or d 90 to 109 (BR90, n = 12) of gestation. Jugular blood samples were collected on d 50, 70, 90, and 109 of gestation and assayed for prolactin and estradiol. Gilts were slaughtered on d 109 of gestation and fetuses were counted and weighed. One row of mammary glands was used for dissection of parenchymal and extraparenchymal tissues, and for biochemical analyses. Tissue from the other row was used for measures of prolactin receptor number and affinity. Concentrations of prolactin were decreased markedly (P < 0.001) at the end of each bromocriptine treatment period compared with controls, but there was no overall treatment effect (P > 0.1) on estradiol concentrations. Extraparenchymal tissue weight of the mammary glands was unaffected by treatments (P > 0.1), but weight of parenchymal tissue, total DNA, and total RNA were lower (P < 0.01) in BR90 than control gilts. The percentage of DM in parenchymal tissue was unaffected by treatments (P > 0.1), but percentage of fat was higher and percentage of protein lower (P < 0.01) in BR90 gilts compared with controls. Cell size, as estimated by the protein:DNA ratio, also was lower (P < 0.01) in the BR90 group. Number and affinity of prolactin receptors in parenchymal tissue were not significantly altered by treatments. In conclusion, there is a specific time period in the second half of gestation, from 90 to 109 d, during which prolactin is essential for normal mammary parenchymal tissue development.

Animals↗
PubMed2000

[Immunological properties of prolactin].

A profound bi-directional interaction exists between the hormone prolactin and the immune system. Even the name "hormone" seems to be inadequate, since prolactin is clearly a growth factor and in fact it functions as an immune co-mitogenic cytokine using autocrine, paracrine and obviously endocrine mechanisms. Prolactin (PRL) stimulates lymphocyte proliferation in response to antigen and mitogens. In addition, prolactin is locally secreted by immune cells, and the pituitary production of prolactin is partially under the control of pro-inflammatory cytokines. These reciprocal influences imply the presence of specific receptors for prolactin in many immune cells, such as lymphocytes and other accessory cells. The PRL-binding to its receptor stimulates the synthesis and secretion of lymphocyte cytokines. In addition, it is a growth factor essential for at least one lymphoid cell line. The PRL-corresponding mRNA has been demonstrated in the cytoplasm of mitogen-stimulated lymphocytes, and the secretion of PRL has been well documented in lymphoid cells. Moreover, PRL acts on NK cells to induce their differentiation to prolactin-activated killer cells (PAK cells) in a dose-dependent way (activation at physiological concentrations, and cytotoxicity inhibition at tenfold higher concentrations). PRL also shows a well known capacity to induce IFN-gamma and IL-2 synthesis, suggesting their participation in the genesis of Th1-responses. These PRL immunological properties strongly support PRL as a cytokine. PRL involvement in both the normal immune response and in many pathological conditions raises important considerations regarding potential diagnostic and therapeutic applications.

Animals↗
PubMed1976

[Prolactin in male reproduction].

Prolactin (PRL), a peptide hormon from the hypophysis, becomes more interesting, since it can be determined by radioimmunassays. The release of prolactin is controlled by two not yet identified factors, the prolactin-releasing-factor and the prolactin-inhibiting-factor. The latter predominantes. Many pharmacological substances can alter the release. The normal serum levels in the man are 6-13 ng/ml. Prolactin affects many organs, f.e. kidney, mamma, ovary, testis, hepar and skin. For clinical tests the raise in the serum levels after TSH or chlorpromacin and the drop after application of 2-brom-alpha-ergocryptin is used. Increased serum levels are found in patients with prolactin-producing tumors. In the male this is followed by disturbances of the sexual potency. Relations between prolactin and male infertility of gynecomastia are not yet known.

Animals↗
PubMedDate not supplied

Antagonism of prolactin binding by cyclosporine A on MCF7 breast tumour cell line.

Cyclosporine A (an immunosuppressive cyclic undercapeptide) acts as an antagonist to prolactin receptors on a breast tumour cell line (MCF7) which is known to express specific prolactin receptors. The competition between cyclosporine A and prolactin to prolactin receptors was demonstrated by measuring the decreased specific 125I-labeled prolactin-binding to prolactin receptors in the presence of increasing concentrations of cyclosporine A. Moreover, cyclosporine A inhibiting effects on the cell growth were investigated in this mammary cancer (MCF) by measuring the cell DNA content with flow cytometry. Our results should prove very useful in understanding the mechanisms of prolactin regulation of DNA synthesis in tumorigenesis of the mammary gland.

Binding, Competitive↗
PubMed1990

Ascorbic acid potentiates the inhibitory effect of dopamine on prolactin release: a putative supplementary agent for PIF.

Dopamine has a catechol group which can be easily oxidized by mild oxidizing agents. Ascorbic acid has been routinely added to a dopamine solution in order to protect it from oxidation. We have examined the effect of ascorbic acid on dopaminergic inhibition of prolactin release. Male rat pituitary cells were dispersed using trypsin and cultured for 5-7 days before experiments. Ascorbic acid did not stimulate nor inhibit prolactin release in both static monolayer culture and dynamic perifusion systems, but potentiated by approximately 100 times the inhibitory effect of dopamine on prolactin release. In order to differentiate chemical protection from potentiation, we tested the potentiation effect of isoascorbic acid which is an epimer of biologically active L-ascorbic acid but is biologically less active. Our results indicated that isoascorbic acid caused less potentiation of the dopaminergic effect on prolactin release than did ascorbic acid. In a perifusion system, a high concentration of dopamine (100 nmol/l) was unable to inhibit prolactin release for a 1 h experimental period, but a low concentration of dopamine (10 nmol/l) plus ascorbic acid (10 mumol/l) inhibited prolactin release for the entire 1 h perifusion period. There is a strong possibility that ascorbic acid may be a physiological supplementary agent for the prolactin-release inhibiting factor (PIF) since the blood concentration of ascorbic acid is rather high (23-85 mumol/l).

Animals↗
PubMed1977

[The effect of several sexual steroids, 2-bromo-ergokryptin and lisurid-hydrogenmaleate an the postpartum concentration of serum prolactin and lactation (author's transl)].

The effect of Ablacton, Estrovis 4000, 2 Brom-alpha-ergokryptin (Cb 154) and of Lisurid-hydrogenmaleate (LHM) on lactation and the serum concentration of prolactin postpartum was studied. 10 normal nursing postpartum patients served as control. LHM was tested in a double blind study compared to placebo. The serum prolactin (PRL) was determined daily for the first 10 postpartum days by radioimmunoassay. Inhibition of lactation was consistent with Cb 154 (89% of the cases). Within two to three days after the onset of treatment with Cb 154 the changes of pregnancy in the breasts had completely subsided. The sexual steroids resulted in inhibition of lactation in 60% of the postpartum patients but mastodynia continued. LHM showed no difference from group taking placebo. The serum prolactin levels postpartum remained as high as a nursing mother's or rose with the administration of steroids. The administration of Cb 154 resulted in a drop of the serum prolactin to non-pregnant levels with in 2 days. The serum prolactin levels under treatment with LHM were not different from the group slowly. In nursing mothers, the stimulus of suckling maintain the pituitary secretion of prolactin as showed by higher serum prolactin levels and a slower decreased to normals than in the non-nursing mothers.

Bromocriptine↗