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PubMedDate not supplied

Prolactin release from perifused human decidual explants; effects of decidual prolactin-releasing factor (PRL-RF) and prolactin release-inhibitory factor (PRL-IF).

The dynamics of prolactin release from human decidual explants were studied under basal conditions, in response to decidual prolactin-releasing factor (PRL-RF), and in response to PRL-RF in the presence of decidual prolactin release-inhibitory factor (PRL-IF) or other factors known to inhibit prolactin release in static cultures. Explants were perifused with medium at a rate of 6 ml/h, and the medium was collected at 5 min intervals. The explants released prolactin for up to 20 h without evidence of cell necrosis, with the rate of prolactin decreasing gradually from 3.9 +/- 0.1 ng/5 min during the first 2 h to 2.2 +/- 0.1 ng/5 min during the last 2 h of exposure. PRL-RF, a 23.5 KMr protein released by the placenta, stimulated a dose-dependent increase in prolactin release from the perifused explants that occurred within the first 5 min of exposure and persisted until the exposure to the releasing factor was discontinued. PRL-IF, a 35-45 K Mr protein released by the decidua, caused a dose-dependent inhibition of PRL-RF-mediated prolactin release. Dibutyryl cAMP, cholera toxin, sn-1, 2-dioctonylglycerol, PMA, and arachidonic acid, which inhibit basal prolactin release from static decidual cultures, also caused a dose-dependent inhibition of prolactin release in response to PRL-RF. In each instance, the maximal dose of the agents tested inhibited PRL-RF-mediated prolactin release by greater than 84 per cent. These results indicate that the stimulation of prolactin by PRL-RF is inhibited by PRL-IF and pharmacologic agents that inhibit basal prolactin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonic Acid↗

PubMed1979

Renal and vascular activity of prolactin preparations. Contamination of prolactin preparations with ADH and implications on renal and vascular prolactin research.

Prolactin, as a "broad spectrum hormone", has been described to exert also vascular and renal actions in laboratory animals and in humans. However, prolactin preparations of various species are contaminated with neurohypophysial hormones (ADH, oxytocin) which possess vascular and renal activities. Antisera against ADH, oxytocin and prolactin are rather specific inactivators of the biologic activity of the respective hormone; the oxytocinasevasopressinase system of pregnancy plasma destroys ADH and oxytocin. Incubation-identification procedures with antisera against ADH, oxytocin and prolactin and with pregnancy plasma revealed that changes in blood pressure, urine flow and urinary osmolarity cannot be ascribed to prolactin per se but to the ADH impurity of prolactin preparations. Furthermore, recent metabolic studies in normally hydrated, overhydrate and dehydrated animals and humans have shown that prolactin does not affect renal water and electrolyte excretion. Thus, earlier reports on vascular and renal activity of prolactin in laboratory animals and humans should be viewed with great caution. Elimination of neurohypophysial hormone impurities of prolactin preparations by incubation with either ADH and oxytocin antisera or with pregnancy plasma provides techniques for better assessment of the real biologic effects of the prolactin molecule.

Animals↗

PubMed1990

Prolactin messenger ribonucleic acid levels, prolactin synthesis, and radioimmunoassayable prolactin during the estrous cycle in the golden Syrian hamster.

The purpose of this study was to observe the molecular dynamics of pituitary prolactin (PRL) gene expression during the estrous cycle of the Golden Syrian hamster. PRL messenger ribonucleic acid (mRNA) levels, PRL synthesis (3H-PRL in the incubation media or incubated pituitary after a 3 hr incubation with 3H-leucine), and radioimmunoassayable (RIA) PRL (in the incubation media or incubated pituitary after the 3 hr incubation) were measured in the morning (0930-1100 hr) on each day of the cycle. We observed that all of these PRL indices declined or did not change from Day 2 to Day 3 of the cycle. From Day 3 to Day 4 (proestrus), however, PRL mRNA levels increased 33-38% and media 3H-PRL increased 32-42%, while there were no significant changes in pituitary 3H-PRL, or RIA-PRL in the media or pituitary. From Day 4 to Day 1 (estrus) there was a reciprocal change in the levels of 3H-PRL in the pituitary vs. the media, with the former increasing 37-50% and the latter decreasing 25-32%. Pituitary RIA-PRL also increased 45-64% from Day 4 to Day 1 while media RIA-PRL did not change. These data are consistent with the following hypothesis: On the morning of proestrus (Day 4) in the hamster, PRL mRNA levels are elevated compared to those on Day 3, signaling an increase in PRL synthesis. This newly synthesized PRL is shunted into a "readily releasable" pool on the morning of Day 4 (contributing to the afternoon surge of serum PRL), and into a "preferentially stored" pool by the morning of Day 1 (for release in response to cervical stimulation and use as a luteotrophin to maintain early pregnancy should fertilization occur).

Animals↗

PubMed1991

Prolactin-deficient GH3B3 cells are defective in the utilization of the endogenous prolactin promoter yet are fully competent to initiate transcription from a transfected prolactin promoter.

Transcription of the prolactin (PRL) gene has been analyzed in wild-type D6, PRL-deficient B3, and revertant r16 GH3 cells. Levels of processed nuclear transcripts from the PRL gene were substantially reduced in the deficient line compared to wild-type cells and returned to greater than wild-type levels in the revertant line. Rare PRL transcripts in the deficient line contained the same 5' end found on transcripts in wild-type and revertant cells as judged by primer extension and S1 nuclease protection assays, implying that the cells are deficient in utilization of the normal wild-type promoter. Deficient cells also contained wild-type levels of the PRL- and growth hormone-specific transcription factor pit-1/GHF-1, and no difference was found in the ability of extracts from wild-type and deficient cells to retard various restriction fragments from both the proximal and the distal PRL promoter regions. The deficient and wild-type cells were equally competent in initiating transcription from a transfected rat PRL promoter containing both the distal and proximal promoter elements. These observations imply that PRL-deficient cells are not defective in a trans-activating factor functioning on these PRL promoter fragments (trans model). Rather, inefficient use of the PRL promoter in the variant cells may reflect an increased methylation state of the PRL gene itself (cis model).

Animals↗

PubMed1989

Depressed pituitary prolactin mRNA, prolactin synthesis, and prolactin storage after light-deprivation in female hamsters is not due to loss of estrous cyclicity alone.

Pituitary prolactin (PRL) cell activity (i.e. PRL messenger ribonucleic acid [mRNA] levels, PRL synthesis, and radioimmunoassayable [RIA]-PRL), and serum RIA-PRL were measured in female golden Syrian hamsters that were (1) light-deprived and then ovariectomized before loss of estrous cyclicity, (2) light-deprived but not yet acyclic, and (3) light-deprived and ovariectomized simultaneously. The results indicate that light-deprivation can decrease PRL cell activity in ovariectomized hamsters but not in animals that continue to cycle. Thus, estrous cyclicity can be said to largely protect PRL cell activity from depressions due to light deprivation. After acyclicity/ovariectomy, however, PRL cell activity is no longer protected and light-deprivation leads to large depressions in PRL mRNA levels, PRL synthesis, and RIA-PRL beyond that caused by acyclicity/ovariectomy alone. As seen in previous studies of total light-deprivation in nonovariectomized female hamsters, we found that removing the pineal gland in conjunction with light-deprivation in ovariectomized hamsters can completely, partially, or fail to restore various measures of PRL cell activity.

Animals↗

PubMed1976

Prolactin stimulation test with perphenazine: an evaluation of plasma prolactin levels and pituitary secretory activity in the rat.

Many investigations of the regulation of prolactin synthesis and release are based on single plasma prolactin determinations. The purpose of the present experiment was to ascertain whether groups of rats (i.e. young or adult, male or female animals, being either intact, gonadectomized or gonadectomized and treated with oestrone), differing in age and/or endocrine status, will react to a single dose of perphenazine by an acute release of pituitary prolactin in proportion to their initial plasma prolactin levels. No consistent relation existed between the classification of the twelve groups of rats into three categories of basal plasma prolactin levels (i.e. less than 20, 25-50, greater than 125 ng/ml) and their response to perphenazine. Even though all groups showed a highly significant increase of plasma prolactin levels the magnitude of the maximum prolactin response at 30 min varied greatly within the groups of one category and thus was not related to the initial prolactin levels. The effect of 14 days of oestrone treatment in increasing plasma prolactin levels in gonadectomized animals was greatest in young and adult male rats, less in young females and not significant in adult females. The results obtained after perphenazine treatment in the latter group made it clear that the effect of oestrogen treatment on prolactin release can be completely blocked by increasing synthesis and/or release of the prolactin-release inhibiting factor (PIF). Since perphenazine induces decrease of pituitary prolactin and a concomitant increase of plasma prolactin levels through lowered PIF-action, the positive effect of oestrogens on prolactin release (as observed in gonadectomized male and young female rats) apparently is caused by a different mode of action. The implications of these findings for the regulation of prolactin release, as affected by the endocrine status of the rat, is discussed. Moreover, comparison of prolactin lost from the pituitary and gained in the circulation of the experimental animals, with amounts of prolactin that were observed to disappear from plasma during the experiment, provided suggestive evidence that the capacity to synthesize and/or eliminate prolactin, after a sudden provoked release of the hormone, differed among the groups. The rates of synthesis by the pituitary, of release from the pituitary into the circulation as well as of elimination of the hormone from the circulation (equally involved in determing actual plasma levels) are thought, therefore, to be far more important for the elucidation of prolactin regulation than single plasma prolactin determinations.

Animals↗

PubMed1992

Prolactin-containing pituitary adenomas. Their characteristics and comparative study with non-prolactin adenomas.

Immunohistochemical study of 130 pituitary adenomas shows that 31% are prolactin-containing adenomas, two-thirds of which are monohormonal adenomas, i.e. prolactin cell adenoma, and one-third are multihormonal adenomas, i.e. mixed growth hormone cell-prolactin cell adenoma and plurihormonal adenoma with prolactin. Clinical symptoms including amenorrhea and galactorrhea are not useful in distinguishing prolactin from non-prolactin adenomas. Serum prolactin concentration of 80 ng/ml is a good cut-off point to distinguish prolactin cell adenoma from non-prolactin adenoma but can not separate many of the multihormonal adenomas from non-prolactin adenomas. Calcification is not only more commonly seen but also more prominent in prolactin-containing adenomas. Spheroid amyloid is present in one prolactin cell adenoma. Immunohistochemistry is specific and reliable in identifying prolactin-containing adenomas. All prolactin cell adenomas and 2/13 multihormonal adenomas show paranuclear staining of prolactin in almost every adenoma cell. The remaining (11/13) multihormonal adenomas show less prolactin cells and diffuse cytoplasmic staining of prolactin. The prolactin staining pattern in the latter group is unique and appears to be indicative of the presence of other hormone(s).

Adenoma↗

PubMed1989

Bovine neurophysin-II stimulates prolactin release without involvement of dopaminergic prolactin-release inhibiting factor receptor in the estradiol-primed male rat.

Neurophysins have been considered to be physiologically inert carrier proteins for the neurohypophysial hormones, oxytocin and vasopressin. We have observed that bovine neurophysin-II indirectly stimulates prolactin release in estradiol-primed male rats. The release of prolactin is regulated by a dual hypothalamic control system, the prolactin-release-inhibiting factor and the prolactin-releasing factor. We have tried to clarify whether neurophysin-II is acting through stimulation of prolactin-releasing factor by eliminating the possibility of dopaminergic prolactin release-inhibiting factor release. Male rats were primed with estradiol and functional dopaminergic prolactin release-inhibiting factor receptors were completely blocked by pretreatment with a large dose of pimozide (3 mg/kg), a dopaminergic receptor blocking agent. The neurophysin-II stimulated prolactin release in the rats which did not have any functional dopaminergic prolactin release-inhibiting factor receptors suggesting that neurophysin-II likely initiates a chain of events which eventually stimulates prolactin-releasing factor release since the possibility of involvement of the dopaminergic prolactin release-inhibiting factor system is eliminated. Opioids are known to be one of a chain of events which transmit external stress into a stimulation of prolactin release. Naloxone, a mu-receptor antagonist, was injected 20 min before neurophysin-II administration into rats which were primed with estradiol and pretreated with pimozide (3 mg/kg), but the naloxone administration did not block the prolactin release stimulated by neurophysin-II injection. This result indicates that opioids are not one of the chain of events between initiation of stimulation by neurophysin-II and prolactin release.

Animals↗

PubMed1992

Involvement of physiological prolactin levels in growth and prolactin receptor content of prostate glands and testes in developing male rats.

We have investigated the role of physiological prolactin levels in the development of prepubertal male rats. Prolactin GH and testosterone levels, as well as body, ventral prostate and testicular weight, have been analysed in both control and bromocriptine-treated rats between 21 and 60 days of life. Furthermore the role of prolactin in the regulation of its own receptors has also been studied during the same period. In control rats, prolactin levels showed a prepubertal peak of secretion at 25 days of age. At this time GH and testosterone levels were low and did not show any significant variation. After this age, prolactin levels increased more gradually; determinations of GH showed great variation with low levels in most of the rats and very high values in the other animals; testosterone levels remained low until day 35 after which they increased. Simultaneously with the serum prolactin peak on day 25, a decrease in prolactin-binding capacity of ventral prostate glands, was observed and a maximum rate of body, prostate and testicular weight gain was obtained. Furthermore, in rats with pharmacologically suppressed serum prolactin levels (lower than 1 microgram/l), prolactin binding to prostate glands as well as the weight of body, ventral prostate and testes were lower than in control animals. When results were expressed in mg prostate or testes/g body weight, testes from 25-day-old treated rats weighed significantly less than controls. The later stages of development, from days 25 to 60, were characterized by an initial decline in serum prolactin levels at 29 days of age which was followed by a continuous increase until adult values were reached. During this period, prostatic prolactin receptors which were at their lowest value at 33 days of age showed a gradual rise parallel with the observed increase in plasma prolactin levels. When testicular tissue was analysed, no changes in prolactin-binding sites caused by sexual maturation were observed. The present results indicate that physiological prolactin secretion has a specific effect on the normal increase in the prostate, testes and body weight and clearly is also implicated in the regulation of its prostatic receptors at the earlier stages of development.

Animals↗

PubMed1976

Prolactin inhibition test with L-dopa: decrease and restoration of plasma prolactin levels in the rat by a peripheral process.

L-DOPA, within 30 min after administration, induced a highly significant decrease of plasma prolactin levels (phase 1) in a number of groups of rats, differing in age and/or endocrine status, apparently by direct inhibition of prolactin release from the pituitary. Three hours after administration of L-DOPA these low plasma prolactin concentrations in treated animals had increased (phase 2) and did not differ significantly from levels in control animals, indicating that the effect of L-DOPA on plasma prolactin levels is only of short duration. During this process some interesting phenomena were observed, especially in the animals treated with oestrone. The elimination rate of prolactin from plasma was very high (t 1/2 = 2.8 min), as indicated by decreasing concentrations of the hormone during phase 1. Pituitary prolactin content did not change during phase 1, suggesting that prolactin synthesis was also stopped. Notwithstanding the high elimination rate, plasma prolactin regained initial concentrations in phase 2, suggesting release of a substantial part of the pituitary prolactin content. The latter,however, remained constant during the whole experiment (i.e. before L-DOPA administration and during phase 1 as well as phase 2). The results suggested another working mechanism of L-DOPA in decreasing plasma prolactin levels, namely by stimulating the uptake of this hormone in the periphery. After the effect of L-DOPA had ceased, most of the prolactin from the periphery returned into the bloodstream, causing a rapid restoration of plasma prolactin levels without substantial release from the pituitary. The nature of the processes responsible for the peripheral uptake of prolactin is discussed.

Animals↗

PubMed1990

Characterization of monoclonal antibodies against ovine prolactin: suitability for use in immunocytochemical analysis of rat prolactin.

The aim of this study was to identify a monoclonal antibody (MAb) suitable for use in the immunocytochemical localization of prolactin in rat tissues. We took advantage of the conservation of certain amino acid sequences in prolactin among species by examining the crossreactivity patterns of five MAb, originally generated to ovine prolactin, with rat prolactin by enzyme-linked immunoassay (ELISA), Western blot analysis, and immunocytochemistry. Two of five antibodies (17D9 and 6F11) showed reactivity with 100 ng of immobilized rat prolactin (NIH RP-3) by ELISA, 6F11 reacting more strongly than 17D9. Only 6F11 reacted with prolactin in lysates of GH4C1 rat pituitary tumor cells by Western blot analysis. When we examined the crossreactivity of the MAb with rat prolactin in monolayer cultures of GH4C1 cells by indirect immunofluorescence, we found that both 17D9 and 6F11 reacted strongly with the cultures. The distribution of staining with 17D9 or 6F11 was coincident with staining with a polyclonal antiserum to rat prolactin. Preabsorption of the antibodies with a 20-fold excess of purified rat prolactin abolished the staining of GH4C1 cell cultures with either antibody. Therefore, we have selected from a series of MAb raised to ovine prolactin two antibodies (17D9 and 6F11) that react specifically with rat prolactin in immunocytochemical studies, whereas 6F11 also reacts strongly with rat prolactin by ELISA and Western blot analysis.

Animals↗

PubMed1976

Relationship between prolactin secretion and hypothalamic prolactin releasing factor in pregnant and puerperium rats.

The present study attempted to elucidate stimulatory factor(s) in the rat hypothalamus which controls prolactin secretion from the anterior pituitary. Rat serum prolactin was elevated so much in late pregnancy that we prepared the hypothalamic extract of late pregnant rats. Prolactin levels in serum and pituitary by radioimmunoassay. After injection of this extract into a lactating rat 48-60 hr after delivery, the serum prolactin level was elevated significantly one to four hr later and the pituitary prolactin level declined two hr later. On the other hand, the hypothalamic extract of normal female rats prepared in a similar manner inhibited prolactin secretion from the anterior pituitary in the lactating rat as described by other authors. These data indicate that the prolactin releasing factor may consist in the hypothalamus of late pregnant rat, and be predominant over the prolactin inhibiting factor during late pregnancy. Prolactin secretion was also investigated in lactating and non-lactating puerperium rats. Prolactin in serum and pituitary declined with days after delivery in non-lactating rats, but not in lactating rats. The presumed factor for such prolactin release in lactating rats is considered to be the prolactin releasing factor.

Animals↗

PubMed1978

Mammary gland prolactin receptor and pituitary prolactin secretion in lactating mice with different lactational performance.

SHN female mice, a high mammary tumour strain, are superior to SLN, a low mammary tumour strain, in lactational performance. Mammary gland prolactin receptor and pituitary prolactin secretion during lactation were compared between these strains. The binding activity, the number of receptor sites per mg tissue and the association constant were measured by the in vitro incubation of mammary gland slices with 125I-labelled bovine prolactin, and the pituitary and plasma levels of prolactin were assayed by homologous radioimmunoassay. There was only a slight difference between strains in any of the parameters for prolactin receptor and for prolactin secretion on either day 4 or day 9 of the first lactation. Almost all the correlation coefficients between each parameter for prolactin receptor and the pituitary or plasma level of prolactin were not statistically significant. These findings suggest that any parameter for prolactin examined in this study is not always directly indicative of lactational performance and further show that the individual variation in the pituitary prolactin secretion during lactation is not so great as to alter the prolactin receptor.

Animals↗

PubMed1991

Somatostatin partially impedes the stimulatory effects of thyrotrophin-releasing hormone and dibutyryl cyclic AMP on prolactin release: prolactin release through multiple routes.

Patterns of prolactin release were examined using stimulating and inhibiting agents. Primary cultured pituitary cells primed with oestrogens were used for perifusion experiments. TRH (100 nmol/l) increased the peak prolactin concentration to 360% of the basal concentration, while TRH, under inhibition by 1 nmol somatostatin/l, raised the peak prolactin concentration to 185% of the basal levels. When the somatostatin concentration was increased to 10, 100 and 1000 nmol/l, TRH still stimulated prolactin release to 128%, 121% and 140% respectively, indicating that concentrations of somatostatin of 10 nmol/l or higher did not further suppress the stimulatory effect of TRH. TRH (1 mumol/l) stimulated prolactin release under the influence of 0 (control), 1, 10, 100 and 1000 nmol dopamine/l (plus 0.1 mmol ascorbic acid/l) to 394, 394, 241, 73 and 68% of the basal concentration respectively, showing that the dopamine concentrations and peak prolactin concentrations induced by TRH have an inverse linear relationship in the range 1-100 nmol dopamine/l. The stimulatory effect of dibutyryl cyclic AMP (dbcAMP) on prolactin release was also tested. The relationship between dbcAMP and somatostatin was similar to that between TRH and somatostatin. When adenohypophyses of male rats were used for perifusion experiments, somatostatin (100 nmol/l) did not inhibit basal prolactin release from the fresh male pituitary in contrast with the primary cultured pituitary cells, but dopamine (1 mumol/l) effectively inhibited prolactin release. In conclusion, (1) oestrogen converts the somatostatin-insensitive route into a somatostatin-sensitive route for basal prolactin release, (2) TRH-induced prolactin release passes through both somatostatin-sensitive and -insensitive routes, (3) dopamine blocks both somatostatin-sensitive and -insensitive routes and (4) cAMP activates both somatostatin-sensitive and -insensitive routes.

Animals↗

PubMed1990

A monoclonal antibody which inhibits the biological activity of rat prolactin, but not prolactin from other species.

Monoclonal antibodies generated to ovine prolactin were screened for their ability to neutralize the biological activity of prolactin from several species. By Western blot analysis, antibody 6F11 cross-reacted strongly with prolactin in homogenates of anterior pituitary glands from squirrel monkey, sheep and rat. In addition, this antibody (1 micrograms IgG/ml) completely inhibited the lactogenic activity of serum or purified prolactin (0.5 ng/ml) from rat, but not prolactin from any other source, in the Nb2 lymphoma bioassay. 6F11 cross-reacted with purified ovine and rat prolactin by enzyme-linked immunosorbentassay (ELISA) and Western blot analysis with similar affinities, suggesting that the 6F11 epitope was common to these peptides. Another monoclonal antibody (17D9, 35 ng IgG/ml) showed the opposite selectivity, completely inhibiting the activity of 0.3 ng/ml ovine prolactin, but not 0.5 ng/ml rat prolactin, in the Nb2 assay. Thus, we have identified monoclonal antibodies which cross-react with both ovine and rat prolactin, but selectively neutralize the lactogenic activity of prolactin from only one species.

Animals↗

PubMed1976

A possible role of cyclic AMP in mediating the effects of thyrotropin-releasing hormone on prolactin release and on prolactin and growth hormone synthesis in pituitary cells in culture.

Thyrotropin-releasing hormone (TRH) has 3 effects on clonal strains of rat pituitary cells in culture (GH-cells). Two long-term effects of TRH on GH-cells, which are measurable after 3 h or longer, have been previously reported; these are an increase in prolactin synthesis and a decrease in growth hormone production. We report here that TRH also stimulates the rapid release of stored intracellular prolactin. We have investigated the role of cyclic AMP as a possible mediator of the effects of TRH on GH-cells. Cyclic AMP concentrations are higher in cells treated with TRH compared with paired controls; a maximum difference of greater than 150% of control values is detected at 15 min if the incubation is performed in serum-free medium in the presence of 1 mM theophylline. The concentration of TRH required to give half-maximum increases in both prolactin release and cyclic AMP accumulation is 0.3 nM; half-maximal increases in prolactin synthesis occur at 3 nM TRH. Exogenous cyclic AMP (1 mM) causes only a slight increase in prolactin release; 8-bromo-cyclic AMP and 8-methylthio-cyclic AMP (1 mM) do not cause significant release. Phosphodiesterase inhibitors (0.3 mM theophylline, 0.03 mM isobutyl-methylxanthine) increase prolactin release but their effects on hormone synthesis are more complicated. Isobutylmethylxanthine, 8-bromo-cyclic AMP and 8-methylthio-cyclic AMP (0.4 MM) increase prolactin synthesis, but do not significantly affect growth hormone synthesis. Theophylline increases the synthesis of both hormones. Dibutyryl cyclic AMP (0.5 mM or more) increases prolactin release and both growth hormone and prolactin synthesis, but equivalent amounts of sodium butyrate have the same effects. We conclude that in GH-cells under carefully defined experimental conditions: 1) TRH causes an increase in intracellular cyclic AMP concentrations; 2) the increase in endogenous cyclic AMP and the effects of phosphodiesterase inhibitors are consistent with a model with cyclic AMP as a mediator of the effects of TRH on prolactin release; however, they do not prove this model, because the interpretation of these results depends on assumptions which may not all be valid; and 3) none of the analogs of cyclic AMP or the phosphodiesterase inhibitors tested mimic the decrease in growth hormone production caused by TRH.

Animals↗

PubMed1976

Cerebrospinal fluid prolactin: a reflection of abnormal prolactin secretion in patients with pituitary tumors.

Cerebrospinal fluid prolactin levels were determined in 33 patients with pituitary disease, 3 pregnant women at term and 30 control subjects. Prolactin which was immunologically similar to the human prolactin standard was detected by radioimmunoassay in the CSF of most of these subjects. Elevated serum and CSF PRL concentrations were found in three pregnant subjects and in twelve patients with putuitary tumors. Ten patients with pituitary tumors had serum PRL concentrations greater than their corresponding CSF PRL levels. A significant correlation was noted between the elevated serum and CSF prolactin levels in the twelve hyperprolactinemic patients which suggested that the CSF prolactin concentration was influenced by the serum PRL level. Two patients with pituitary tumor however, had CSF prolactin concentrations higher than their serum levels, which suggested that direct secretion of prolactin from the tumor to the CSF can also occur. Three patients with chromophobe adenomas had normal serum PRL concentrations and elevated CSF prolactin levels which differentiated them from fifteen patients with the primary empty sella syndrome who had normal serum and CSF prolactin levels. The finding of normal CSF prolactin levels in the primary empty sella patients argues against the postulate that the diaphragma sellae significantly influences CSF pituitary peptide concentrations.

Acromegaly↗

PubMed1991

Inhibitory control of prolactin and Pit-1 gene promoters by dopamine. Dual signaling pathways required for D2 receptor-regulated expression of the prolactin gene.

Transcription of the prolactin gene is suppressed by dopaminergic activation of D2 receptors in pituitary lactotrophs. The mechanism of signal transduction at the nuclear level and the cell surface was examined in the dopamine-responsive GH4ZR7 cell line. Dopamine treatment caused a 40-50% decrease in endogenous prolactin mRNA that was specifically blocked by addition of (-)-sulpiride. To define dopamine-responsive elements, plasmids containing 5'-regulatory regions of the prolactin gene fused to the coding sequences for luciferase were transiently or stably transfected into GH4ZR7 cells. Chimeric transcripts initiated at the authentic transcription start site were regulated in a promoter-selective manner; dopamine or the agonist bromocryptine inhibited prolactin promoter (position -422) activity by 70%, but had no regulatory effects on other cellular or viral promoters. A shorter prolactin promoter (position -78) or a prolactin TATAA box linked to heterologous binding sites for transcription factor Pit-1 was sufficient to confer dopamine inhibition (40%). In addition to the prolactin promoter, we found that dopamine inhibited transcriptional activity of the Pit-1 promoter (positions -258 to +8) by 60%. Surprisingly, deletion of two cAMP response elements in the Pit-1 promoter only partially eliminated dopamine responsiveness. These data suggest that sequences in the Pit-1 promoter between positions -92 and +8, which include an autoregulatory Pit-1-binding site and the TATAA box, are sufficient for negative regulation. In this study, we also examined the signal transduction pathways that link D2 receptor activation and the inhibition of prolactin gene transcription. We found, as suggested in earlier studies, that a dopamine-dependent decrease in cAMP may be important for mediating negative regulation of transcription. However, high extracellular K+ concentrations that prevent dopamine effects on membrane potential and [Ca2+]i, but not cAMP levels, completely blocked dopamine regulation of the prolactin promoter. This suggests that two distinct signaling pathways initiated at D2 receptors may be required for transcriptional regulation of the prolactin gene.

Bromocriptine↗