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Prolactin in the circulation of chronically catheterised piglet foetuses and pregnant sows, and the effect of thyrotrophin-releasing hormone.

We chronically catheterised 12 piglet foetuses and 11 sows to determine the changes in circulating concentrations of prolactin during the last 2 weeks of gestation. Prolactin levels were measured by homologous radioimmunoassay and were found to average 2.12 +/- 0.23 ng . ml-1 in the foetuses and 4.19 +/- 0.84 ng . ml-1 in the sows. Foetal concentrations of prolactin increased significantly during the time period of the study. There was no change in maternal concentrations over the corresponding time. Injection of 5 micrograms TRH into 7 foetuses increased the plasma concentrations of prolactin in 6 animals, produced no apparent change in the seventh foetus and did not affect maternal concentrations of prolactin. The magnitude of the maximum response of TRH of the younger foetuses (less than 107 days delta = 0.7, 1.3, 4.2 ng . ml-1) was substantially less than that of the foetuses prior to term (greater than 107 days delta = 6.4, 21.7, 27.5 ng . ml-1). Injection of saline and the haemorrhage of blood sampling produced no significant change in the initial concentration of prolactin. We conclude that prolactin is present in the circulation of the pig foetus, that it is produced endogenously in lower concentrations than in the pregnant sow and that the foetal responsiveness to TRH stimulation increases towards the end of gestation.

Animals↗

Mechanism of serotonin effects on prolactin and growth hormone secretion in domestic fowl.

Brain serotonin levels were increased in immature chickens by ip injection of pargyline (75 mg/kg) and clorgyline (5 mg/kg) and by L-tryptophan (100 mg/kg) and imipramine (10 mg/kg) treatment. These treatments increased the circulating prolactin level and reduced the concentration of plasma growth hormone (GH). Treatment with para-chlorophenylalanine (PCPA, 100 mg/kg) reduced the brain serotonin content and the level of plasma prolactin. Treatment with these drugs in vivo similarly affected the basal level of prolactin release from pituitary glands in vitro, although it did not affect the basal level of GH release. The in vitro responsiveness of the pituitary gland to hypothalamic stimuli eliciting prolactin secretion was increased by in vivo pargyline and combined tryptophan: imipramine treatment but reduced by PCPA administration. The in vitro GH response to hypothalamic stimulation was reduced after the in vivo injection of pargyline, clorgyline and tryptophan: imipramine. The hypothalami from clorgyline and tryptophan: imipramine treated birds induced a greater stimulation of in vitro prolactin secretion from control pituitary glands than hypothalami from controls birds, whereas the GH releasing activity was reduced. These results suggest that serotonin stimulates prolactin secretion in chickens by increasing pituitary responsiveness to hypothalamic releasing factors and by increasing the prolactin releasing activity of the hypothalamus. Serotonin appears to suppress GH secretion by reducing pituitary sensitivity to releasing factors and by reducing hypothalamic GH releasing activity.

Animals↗

Danazol and prolactin status in patients with endometriosis.

A group of 55 women with endometriosis was studied before and during danazol therapy. An unexpectedly high proportion (36%) had a raised serum prolactin level before treatment which was reduced after 50 days of danazol (before treatment 783 +/- 333 mU/l; on danazol 243 +/- 113 mU/l, P less than 0.001). In contrast patients with normal serum prolactin levels showed no significant drop on danazol therapy. In all patients serum oestradiol was significantly reduced during treatment (before treatment 449 +/- 188 pmol/l; on danazol 207 +/- 117 pmol/l, P less than 0.001). In one patient with hyperprolactinaemia danazol reduced both basal and stimulated prolactin levels, whereas in 5 women with normal prolactin levels we could detect no gross alteration in metoclopramide or TRH stimulated prolactin levels associated with danazol therapy. The possibility that normalisation of raised prolactin levels may be secondary to reduced oestrogens and that patients with endometriosis have an increased sensitivity to oestrogen-induced prolactin secretion is discussed.

Danazol↗

Changes in mRNA levels of a pituitary-specific trans-acting factor, Pit-1, and prolactin during the rat estrous cycle.

The present study examined the changes in mRNA levels of a pituitary-specific trans-acting factor, Pit-1, and prolactin during the rat estrous cycle. Total cytoplasmic RNA was analyzed by Northern blot and slot-blot hybridization to examine the prolactin mRNA level. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to examine the Pit-1 mRNA level. Proestrous and estrous prolactin mRNA levels were significantly higher than the metestrous and diestrous levels, whereas Pit-1 mRNA levels of the estrous and metestrous stages were about two- to threefold higher than those of the proestrous and diestrous stages. Proestrous Pit-1 mRNA levels increased gradually from 10.00 h to 20.00 h, while prolactin mRNA levels slightly decreased until 14.00 h but increased later until 20.00 h. During the rat estrous cycle, especially in the afternoon of the proestrous day, changes of prolactin mRNA levels seem to follow a prior increase of Pit-1 mRNA. Therefore, Pit-1 may be partly involved in the regulation of prolactin gene expression according to the rat estrous cycle. Estradiol administration to ovariectomized rats significantly increased both the mRNA levels of prolactin and Pit-1, which suggests that the gene expression of Pit-1 is regulated by estrogen through indirect extracellular pathways.

Animals↗

Effect of modified brain histamine contents on prolactin and thyrotropin secretion in male rats.

Effects of modified brain histamine contents on thyrotropin and prolactin secretion were studied in male rats. Under basal conditions the histamine content in the hypothalamus was approximately 8-10-fold higher than that in the striatum and the rest of the brain. L-histidine (1000 mg/kg, ip), a histamine precursor, and metoprine (20 mg/kg, ip), an inhibitor of histamine methyltransferase, elevated histamine content in the brain by 65% and 167%, respectively. When the treatments were given together an additive effect (119-250% increase) on brain histamine was observed. Metoprine significantly decreased serum prolactin levels, while L-histidine had no effect. This effect of metoprine was not modified by treatment with L-histidine. Thus, metoprine has an inhibitory effect on prolactin secretion that is not related to elevated brain histamine contents. The increased brain histamine content after L-histidine treatment had no effect on prolactin secretion. Basal levels of serum thyrotropin were decreased by both L-histidine and metoprine, L-histidine being more potent. In rats treated with alpha-fluoromethylhistidine, an inhibitor of L-histidine decarboxylase, the cold-induced (rats kept for 60 min at +4 degrees C) thyrotropin secretion was increased while the stress-induced prolactin secretion was decreased. In these rats, metoprine did not affect thyrotropin release but blunted the prolactin response. In conclusion, endogenous histamine inhibits thyrotropin secretion but does not affect prolactin release. Owing to its other effects, metoprine is not suitable as a tool to elevate endogenous histamine contents in the brain, at least when the regulation of anterior pituitary hormone release is being studied.

Animals↗

Circulating endothelin-3 and prolactin concentrations in healthy lactating women during the early puerperium.

OBJECTIVE: To study the association between the circulating concentrations of endothelin-3 and prolactin in the early puerperium. DESIGN: Prospective clinical study, including twenty-five healthy puerperal women breast-feeding their healthy full-term infants. METHODS: Venous blood was drawn on day 1 and 4 post partum, and plasma endothelin-3 and serum prolactin were determined. RESULTS: Circulating endothelin-3 and prolactin levels on day 4 did not differ significantly from the corresponding levels on day 1. However, a significant negative correlation was found on day 4 between endothelin-3 and prolactin values (r = -0.688, P < 0.001) and an even stronger negative association existed between the net change in endothelin-3 from days 1 to 4 and the corresponding change in prolactin values (r = -0.732, P < 0.001). CONCLUSIONS: On the fourth day post partum, lactating healthy women show negative correlation between circulating endothelin-3 and prolactin levels. Whether this indicates a role for endothelin-3 in the control of prolactin secretion in the post partum period remains to be clarified.

Endothelin-3↗

Serum prolactin concentrations in mangabey (Cercocebus atys lunulatus) and patas (Erythrocebus patas) monkeys in response to stress, ketamine, TRH, sulpiride and levodopa.

An homologous radioimmunoassay for human serum prolactin was validated to measure serum prolactin in 10 mangabey and 7 patas monkeys. Mean basal levels of serum prolactin were almost identical in the males of both species and in immature and mature males. However, basal levels were higher in females than in males. Serum prolactin was enhanced by stress, i.v. injection of TRH and intramuscular injection of a potent dopamine antagonist (sulpiride). The rise in serum prolactin observed after i.m. injection of ketamine hydrochloride used as anaesthetic was of small amplitude and short duration. Oral administration of levodopa was followed by a significant fall in serum prolactin. Sexual maturity did not influence the responses to TRH or sulpiride. The mangabeys were more sensitive to sulpiride but less sensitive to levodopa than were the patas monkeys. The variations in serum prolactin levels observed in these monkeys under the influence of stress, TRH, sulpiride and levodopa are similar to those observed in man to the same stimuli, although the experimental conditions were quite different.

Animals↗

Isolation and characterization of turkey prolactin.

Prolactin from frozen turkey pituitary glands was purified by alkaline ethanol extraction of the pituitary residue after pre-extractions of the gonadotrophins and GH, followed by gel filtration on Sephadex G-100 and DEAE-cellulose column chromatography at different pH. A specific radioligand--receptor assay for ovine prolactin was used to locate the activity in eluates after column chromatography and gel filtration. The potency of the highly purified turkey prolactin was characterized by a radioligand--receptor assay to be 3.40 i.u./mg and by a heterologous radioimmunoassay to be 35 i.u./mg as compared to purified ovine prolactin as standard. The yield of turkey prolactin was 3 mg/100 g frozen pituitary glands. The purified turkey prolactin consisted of three protein bands upon polyacrylamide gel electrophoresis and the molecular weight was estimated to be 22000 by SDS--polyacrylamide gel electrophoresis. Turkey prolactin was rich in aspartic acid, glutamic acid and leucine, but lacking in methionine.

Amino Acids↗

Long-term rhythms of testicular volume and plasma prolactin concentrations in rams reared for 3 years in constant photoperiod.

Two groups of 6 rams were kept under constant photoperiod consisting of short days (8 h light (L): 16 h dark (D); Group S) and long days (16 h L:8 h D; Group L) from 4 to 38 months of age. Five other rams were reared under a photoperiod representative of that occurring naturally (Group N). Testis size and plasma prolactin concentrations were obtained weekly. These data were subjected to time series analysis. The results indicated that there were persistent periodic excursions in both parameters measured. In Group N, the average cycle length for both testis volume and plasma prolactin was about 1 year and the peaks in plasma prolactin preceded those in testis volume by about 18 weeks. Rams from Group L also showed rhythmical changes in these parameters with periodicities of around 35 weeks and it is suggested that these cyclic changes may constitute true endogenous circannual rhythms; again the prolactin peaks preceded those of testis volume by about 18 weeks. Overall, rams from Group S had excursions of testis growth of a similar magnitude to those of Group L but the changes were less regular than those of Group L. Plasma prolactin was significantly lower in Group S than in Group L and there was little evidence for rhythmicity. It is proposed on the basis of the temporal relationship between peaks of prolactin and testis volume in Groups N and L, that prolactin may play a role in the timing of the reproductive cycle in the ram.

Animals↗

Seasonal and circadian patterns of circulating prolactin during lactation and seasonal quiescence in the tammar, Macropus eugenii.

Prolactin was measured in peripheral plasma of female tammars once a week for 14 months and every 2 months it was measured in a subgroup of 7 tammars at hourly intervals for 28 h to determine short-term changes in concentration. During the course of the study 6 females gave birth in January/February and reared their young to weaning in October-November, while another 4 gave birth 1.5-3.0 months later and weaned their young in November-December. Concentrations of prolactin were less than 40 ng/ml in a non-lactating animal and for the first 140 days of lactation in the others. Between 140 and 180 days of lactation the concentrations of prolactin fluctuated between 10 and greater than 100 ng/ml and thereafter remained high until the young vacated the pouch for the last time at about 250 days. After pouch exit the concentrations declined to about 40 ng/ml even though lactation continued for a further 21-35 days. Although the short-term patterns of prolactin concentrations showed no consistent relationship between light-dark phases there was an increase in the magnitude and duration of peaks of plasma prolactin which correlated with the stage of lactation. Removal of pouch young aged between 203 and 242 days for 24 h resulted in a rapid decrease in plasma prolactin concentration which was reversed when the young was returned to the pouch, indicating that the high levels of prolactin in the second half of lactation may be maintained by the sucking stimulus of the pouch young. This period of lactation, therefore, may be equated with lactation in eutherians, but there appears to be no eutherian equivalent to early lactation in the tammar.

Animals↗

Ovarian and feto-placental factors and the regulation of prolactin release during pregnancy in the rat.

Administration of progesterone (5 or 10 mg) to pregnant rats increased serum prolactin significantly on the afternoon of Days 4, 6, 7 and 8 of pregnancy, but had no effect on later days. On Day 10 progesterone administration increased serum prolactin only in rats treated with oestrogen the day before. A similar treatment with oestrogen and progesterone was unable to stimulate secretion on the afternoon of Day 13 of pregnancy. In rats from which the corpora lutea had been unilaterally removed and hence endogenous progesterone levels were 50% of the normal values, or in those that carried 4 conceptuses, progesterone treatment after oestradiol priming was partly effective in inducing prolactin release on Day 13. However, in rats ovariectomized, with bilateral excision of the corpora lutea, or with 2 conceptuses left, treatment with ovarian steroids markedly increased serum prolactin values. By Day 13 all the rats from the ovariectomized group or with bilateral excision of the corpora lutea had aborted. On Day 13, therefore, the high serum concentrations of feto-placental factors and of progesterone are responsible for the blockade of the spontaneous and ovarian steroid-induced prolactin release. On the other hand, on Day 16 of pregnancy the decrease of circulating progesterone by excision of the corpora lutea or by ovariectomy followed by oestradiol treatment significantly increased serum prolactin on Day 17. Removal of all the conceptuses did not modify the effects of these treatments. The present results demonstrate different roles of progesterone upon the control of prolactin secretion. After a stimulatory action during the first days of pregnancy, there is a change to an inhibitory control at the end of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of photoperiod on LH, FSH, prolactin and melatonin patterns in ovariectomized prepubertal heifers.

Angus and Angus crossbred prepubertal heifers were ovariectomized and randomly assigned to either increasing light simulating the photoperiod of the vernal equinox to the summer solstice (I) or decreasing light simulating the photoperiod of the autumnal equinox to the winter solstice (D) for 43 degrees N latitude. Three blood samples were taken each week for 14 weeks, the first at 11:00 h and two others 2 days later, 1 h before lights on (dark), 1 h before lights off (light). At the end of 14 weeks 4 heifers from each treatment group were cannulated and samples were taken for 12 h at 15-min intervals, 6 h in the light and 6 h in the dark. All sera were assayed for LH, FSH and prolactin. In addition, the samples taken at 15-min intervals were assayed for melatonin. In samples taken weekly at 11:00 h circulating concentrations of LH and prolactin were higher among animals in Group I, while FSH concentrations were not different between Groups D and I. In samples collected weekly in the light or the dark, LH and prolactin concentrations were higher in Group I animals. However, prolactin concentrations were higher and LH concentrations tended to be higher in samples taken in the dark. FSH concentrations were not different between either D or I or dark and light. In samples taken at 15-min intervals the prolactin baseline was higher and pulse amplitude tended to be higher for Group I animals. Neither LH nor FSH pulse characteristics differed between I and D; however, LH baseline and LH pulse amplitude were higher in the dark. Melatonin pulse amplitude was higher among animals in Group D and higher in serum collected in the dark. These results suggest that photoperiod alters circulating concentrations of LH and prolactin and alters pulsatile release of LH, prolactin and melatonin in the prepubertal heifer.

Animals↗

Suckling-induced prolactin release potentiates mifepristone-induced lactogenesis in pregnant rats.

Suckling, starting at 19:00 h on Day 18 of pregnancy, induced a significant increase in serum prolactin concentration at 20:00 h on Day 19 of pregnancy, but no increase in mammary gland casein or lactose content. Mifepristone (2 mg/kg) injection at 08:00 h on Day 19 of pregnancy induced significant increases in casein, but not in lactose, 24 h after administration. Mifepristone alone did not induce prolactin secretion, indicating that lactogenesis was induced by placental lactogen in the absence of progesterone action. When mifepristone was injected into suckling rats, serum prolactin concentrations were higher than in the untreated suckling rats. Casein in these rats increased significantly 12 h after mifepristone administration and lactose at 24 h after. If the suckling mifepristone-treated rats were given two injections of bromocriptine (1.5 mg/kg) at 12:00 h on Days 18 and 19 of pregnancy, serum prolactin concentrations were not increased by suckling, but casein and lactose concentrations in the mammary gland showed values similar to those obtained in the mifepristone-treated non-suckling rats. Mifepristone can therefore potentiate suckling-induced prolactin release in pregnant rats, demonstrating a direct central inhibitory action of progesterone on prolactin secretion. This suckling-induced prolactin secretion, unable to induce casein or lactose synthesis in the presence of progesterone, enhanced significantly synthesis of these milk components in the absence of progesterone action (rats treated with mifepristone). Fatty acid synthase, which is stimulated by the suckling stimulus in lactating rats, was not modified by mifepristone or suckling in pregnant rats.

Animals↗

Expression of prolactin gene in incubating hens.

Steady-state levels of the 1.38-kb mRNA encoding the prolactin prohormone, measured by northern and dot blotting using a radioactive cDNA probe, rose 10-fold with concomitant increases in concentrations of prolactin in anterior pituitary and plasma from non-incubating to incubating stages in Gifujidori bantam hens. Daily injections of a low dose of thyrotrophin-releasing hormone (TRH, 0.25 micrograms/kg) for 4 days caused no changes in the concentrations of prolactin of the mRNA, but a high dose (2.5 micrograms/kg) of TRH did induce a significant increase in prolactin mRNA levels compared to saline controls. The results suggest that gene expression for prolactin increases substantially during the incubation period and TRH may contribute, at least in part, to the increase in transcription of prolactin mRNA for prolactin biosynthesis in Gifujidori bantam hens.

Animals↗

Prolactin enhances uteroglobin gene expression by uteri of immature rabbits.

The effect of prolactin on uteroglobin production by immature rabbits was studied with neonatal (1 day old) and juvenile (14 days old) does. The animals were divided into 11 treatment groups for each age category and exposed to a 9-day injection protocol. Each day the animals received a subcutaneous injection of oestradiol-17 beta and/or ovine prolactin and/or progesterone, or were sham-injected. Juvenile animals, which received 100 micrograms oestradiol/kg 24 h-1, plus progesterone or plus prolactin and progesterone, produced detectable amounts of uteroglobin in the uterine secretions (0.034 +/- 0.010 mg uteroglobin/mg total protein and 0.098 +/- 0.03 l mg uteroglobin/mg total protein, respectively). None of the animals in the other juvenile treatment groups or any of the neonatal groups produced uteroglobin. From this survey it was apparent that uteroglobin secretion could be induced by exogenous oestradiol and progesterone in rabbits treated as early as 14 days of age, and that the added supplementation of prolactin enhanced the response to the ovarian steroids. As a result, additional juvenile animals were injected with 100 micrograms oestradiol +/- prolactin + progesterone and the effects of these two treatments were quantitated as follows: uteroglobin mRNA levels by slot-blot hybridization; endometrial surface area by computerized image analysis; and oestrogen, progesterone and prolactin receptors by immunocytochemistry. Prolactin modified the response of the juvenile rabbit uterus to oestradiol + progesterone for all parameters tested.

Animals↗

Effects of maintaining solstice light and temperature on reproductive activity, coat growth, plasma prolactin and melatonin in goats.

Interactive effects of light and temperature on aspects of seasonality were studied in female British Saanen dairy goats. Four groups of adult non-pregnant non-lactating goats (n = 5) were housed under the following conditions: controls (July-June): natural photoperiod and temperature; group 1 (July-December): long days (16 h light: 8 h dark) and natural temperature; group 2 (July-December): long days and average summer temperature (17.6 degrees C); group 3 (December-June): short days (8 h light: 16 h dark) and winter temperature (8.4 degrees C). Plasma prolactin and progesterone were measured once a week, circadian changes in prolactin and melatonin were determined in December and May, and coat development was assessed. Seasonal variation in prolactin was influenced by manipulation of both daylength and temperature. In group 1, prolactin concentrations decreased as the environmental temperature decreased, despite maintenance of long days. When light and temperature were maintained under summer (group 2) and winter (group 3) conditions, prolactin remained relatively constant, although at different high and low set points, respectively, but with indications of a seasonal rhythm. An asymptotic relationship between prolactin and temperature was maintained under all daylengths. The circadian pattern of melatonin was related to daylength and was not influenced significantly by temperature. Onset of oestrus was unaltered. In group 3 (maintained winter solstice light and temperature), anoestrus was delayed (P < 0.05) from a median control date of 17 March to a median date of 28 April. Winter coat development was delayed in group 1; group 2 showed premature moulting of the winter coat; and in group 3, development of the summer coat was delayed. The results imply that temperature modifies the influence of daylength on prolactin secretion and hair follicle growth by mechanisms that do not involve melatonin.

Analysis of Variance↗

Concentrations of prolactin in serial blood samples from goats before, during and after milking throughout lactation.

Two experiments are described in which prolactin was measured in (a) serial blood samples taken at monthly intervals (April-November) from six lactating goats before, during and after milking and (b) in similar blood samples taken on days 2, 7 and 12 after parturition. The quantity of prolactin released at milking (April-August) varied both between goats and within the individual goat. No correlation was found between the duration of milking and the quantity of prolactin released into the circulation (r equals minus 0-24, P greater than 0-1) or the average concentration of prolactin found at milking (April-August) and the average daily milk yield of the individual goat (r equals minus 0-57, P greater than 0-1). No evidence was found for a release of prolactin conditioned by events normally preceding milking. The results showed a correlation between the average concentration of prolactin released at milking each month and the average milk yield of the six goats (r equals 0-67, P smaller than 0-05). The physiological significance of this correlation is discussed. No correlation was found between the average concentration of prolactin released during early lactation and the average milk yield of the goats (r equals 0-36, P greater than 0-1).

Animals↗

Effects of castration and gonadal steroids on serum luteinizing hormone and prolactin in old and young rats.

Changes in serum LH and prolactin concentrations in response to bilateral gonadectomy and gonadal steroid replacement were measured in mature young (4-6 months) and old (23-30 months) female and male Long-Evans rats. On day 13 after gonadectomy, female rats were injected with oestradiol benzoate (OB) and male rats with testosterone propionate (TP) for a period of 12 days. They were then permitted a recovery period of 6 weeks. Serum prolactin and LH concentrations were measured by radioimmunassay in single blood samples taken at various intervals before and after gonadectomy and during and after steroid treatment. Serum LH levels were about the same in intact young old female rats, but after ovariectomy LH rose several fold higher in young than in old remale rats. In male rats, after orchidetomy the increase in serum LH was greater in young than in old rats. Oestradiol benzoate and TP injections into female and male young and old rats produced variable effects on LH release. Serum prolactin concentrations were approximately six times higher in old intact than in young intact female rats, and after ovariectomy showed a much greater percentage reduction in old than in young female rats. Administration OB produced a greater absolute increase in serum prolactin in old than in young female rats. Serum prolactin values were about the same in old and young male rats, and the effects of castration and TP administration on serum prolactin were not markedly different in the two age groups. These results indicate that old female and male rats are less capable of releasing LH than young rats of both sexes, but old females release more prolactin than young females.

Aging↗