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Prolactin has been separated from growth hormone (GH) in extracts from sheep and cattle pituitaries, but not when human pituitaries were used. The prolactin activity found in most human growth hormone (HGH) preparations (Li & Liu, 1964; Forsyth, Folley & Chadwick, 1965) supports the hypothesis that HGH and human prolactin (H-Pr) are biologically and immunologically related and suggests that both activities reside in the same molecule (Irie & Barrett, 1962). However, Chen & Wilhelmi (1964) have reported that prolactin activity can be separated from that of GH by chromatography. Moreover, Pasteels, Brauman & Brauman (1963), using tissue cultures of human pituitary cells, found a rapid decrease of GH activity in the medium but an increase in prolactin activity. The present report describes the immunological properties of a human prolactin preparation (Apostolakis, 1965) more potent than any previous preparation.
The activities of batches XVI-R8 and XVII-R8 of human prolactin
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each dam were randomly separated ( n =12 pups). On day 21 of lactation, dams' serum prolactin (PRL) levels were measured by specific RIA using reagents supplied by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD, NIH
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SUMMARY
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. < 20, 25–50, > 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 determining actual plasma levels) are thought, therefore, to be far more important for the elucidation of prolactin regulation than single plasma prolactin determinations.
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Reports in recent years that normal levels of human chorionic somato-mammotrophin (HCS) in cases of threatened abortion are associated with continuation of pregnancy (Genazzani, Aubert, Casoli, Fioretti & Felber, 1969; Singer, Desjardins & Friesen, 1970; Niven, Landon & Chard, 1972) have led to the suggestion that lactogenic hormones may play a role in the maintenance of pregnancy. Sheep prolactin at a concentration of 10 μg/ml has been shown to exert a marked inhibitory effect on myometrial activity in pregnant guinea-pigs (Manku & Horrobin, 1973), rats primed with oestrogen and progesterone (Horrobin, Lipton, Muiruri, Manku, Bramley & Burstyn, 1973), as well as in non-pregnant human myometrium (Mugambi, Mati, Thairu & Muriuki, 1973). In the present study we show that sheep pituitary prolactin at a dose of 40 μg/ml exerts a less inhibitory effect on pregnant rabbit myometrium than in the species quoted above.
Two parallel myometrial strips were obtained from the
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Abstract
The present study addresses the role of prolactin as a regulator of migratory fattening in European quail (Coturnix coturnix). Plasma prolactin levels in captive birds undergoing migratory fattening in an outdoor aviary and in the laboratory were measured by radioimmunoassay with an antibody raised against recombinant-derived chicken prolactin. No strong association between prolactin and migratory fattening was apparent, and prolactin levels were more closely related to daylength, with the highest concentrations being reached on long days. Plasma prolactin profiles were similar in intact and castrated male quail. Prolactin was secreted in a daily rhythm, with the highest concentrations occurring early in the photophase. However, when birds were food-restricted for 50 days during a migratory phase, there was no difference in fat deposition between birds food-deprived for the first half of the daily photophase compared with those deprived for the second half. Fattening was reduced in the food-restricted birds relative to ad libitum-fed controls, but there was no difference in plasma prolactin levels between the groups. Injections of ovine prolactin (4 mg/kg) significantly increased food intake and body mass of birds maintained on long days, but there were no differences in fattening between birds injected in the morning compared with those injected in the afternoon. Collectively, these results do not support a major role for prolactin in the regulation of migratory fat deposition in European quail.
Journal of Endocrinology (1995) 146, 71–79
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ABSTRACT
The interactions between broody behaviour and changes in concentrations of plasma prolactin and LH were investigated in bantam hens. Adoption of newly hatched chicks caused incubating hens to leave their nests and prevented plasma prolactin decreasing as rapidly as in hens deprived of their nests and not given chicks. Further, the hens allowed to rear chicks came back into lay later (P< 0·001) than the hens not allowed chicks. Plasma prolactin decreased and plasma LH increased in hens deprived of their nests: these changes were reversed when the hens re-nested. The changes in plasma LH and prolactin in nest-deprived and re-nesting birds were not always synchronous; this was particularly clear immediately after nest deprivation when the increase in plasma LH preceded the decrease in the plasma prolactin. Readiness to incubate disappeared between 48 and 72 h after nest deprivation and corresponded with the time when plasma prolactin decreased to baseline values. Administration of ovine prolactin depressed (P<0·01) the initial increase in plasma LH after nest deprivation, but repeated administration of prolactin for up to 72 h failed to suppress plasma LH to the values found in incubating hens. Repeated administration of ovine prolactin at 5- to 8-h intervals for 72 h maintained readiness to incubate in nest-deprived hens. It is concluded that the secretion of prolactin in broody hens is facilitated by the presence of chicks and that increased concentrations of plasma prolactin maintain incubation behaviour. In incubating hens the secretion of LH and prolactin may be partly regulated independently. In addition, LH secretion may also be inhibited by increased plasma prolactin.
J. Endocr. (1988) 118, 279–286
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SUMMARY
Ovine 125I-labelled prolactin was incubated with a membrane-rich particulate fraction of mouse mammary gland and bound hormone was separated by centrifugation and washing. The experiments identified two types of binding activity: total binding and specific binding, the fraction of the total which could be displaced competitively by native prolactin but not by a number of other polypeptides. Two other lactogenic hormones, human chorionic somato-mammotrophin and human growth hormone, displaced 125I-labelled prolactin in proportion to their known intrinsic lactogenic activities. Binding of 125I-labelled prolactin was complete within 20 min at 4 or 37 °C. Scatchard analysis of the binding indicated an apparent dissociation constant (Kd ) of approximately 9 × 10−9 mol/l and a concentration of binding sites of 15·5 × 10−13 mol/mg particulate protein. The greatest rate of specific displacement of bound 125I-labelled prolactin was observed at concentrations of prolactin between 50 and 250 ng/ml, a concentration range near the mid-point of the dose—response curve of casein induction in intact mammary cells. The saturating concentration of prolactin for specific binding to mammary particles was similar to that for casein induction in intact cells. The prolactin binding activity was sensitive to treatment with trypsin or heating at 70 °C, indicating its protein nature. These properties of the mammary prolactin binding activity are those required of a receptor for prolactin or other lactogens. Prolactin-specific binding activity was also found in particles from mouse liver, kidney, and midbrain and from the ovary, adrenal, and seminal vesicle of the rat. These results suggest a fairly widespread tissue distribution of the prolactin receptor, and potentially implicate prolactin in the hormonal regulation of these organs.
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SUMMARY
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 (t½ = 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.
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SUMMARY
Perphenazine has previously been shown to stimulate prolactin secretion in intact and to a lesser degree in ovariectomized virgin female rats. The question whether the oversecretion of gonadotrophins (follicle-stimulating hormone and luteinizing hormone) occurring in ovariectomized animals interferes with the ability of the pituitary cells to secrete prolactin was investigated in sham-operated and ovariectomized rats after separate and combined treatment with methallibure (ICI-33828, a non-steroidal gonadotrophin suppressor) and perphenazine which served as a prolactin releaser. Pituitary and serum prolactin were measured simultaneously by radioimmunoassay. Serum prolactin detected at the end of 5 days' treatment with perphenazine (5 mg/kg/day, s.c.) was found to be increased (81 ng/ml) compared with controls (29 ng/ml). Similar treatment given to ovariectomized animals increased serum prolactin levels from 13·7 ng/ml to only 27 ng/ml. Although high doses of methallibure alone (20 mg/kg/day, s.c.) given to ovariectomized rats for 17 days restored prolactin secretion to the levels occurring in intact non-treated animals, a dose of 10 mg was ineffective. However, when 10 mg methallibure were given to perphenazine-treated ovariectomized rats, serum prolactin rose again to 80·1 ng/ml.
These results provide substantial evidence that, when the pituitary is secreting high amounts of gonadotrophin, its prolactin secretion is reduced and its ability to secrete prolactin after perphenazine challenge is limited. Once the gonadotrophic oversecretion is suppressed, more prolactin is secreted and the pituitary can again secrete high amounts of prolactin when challenged by perphenazine. The results show that in rats there exists an antagonism between gonadotrophin and prolactin secretion.
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Considerable indirect evidence exists that certain drugs, including phenothiazine derivatives, stimulate the release of prolactin from the anterior pituitary (see review by Meites, Nicoll & Talwalker, 1963). As a direct test of this hypothesis a radioimmunoassay for sheep prolactin (Bryant & Greenwood, 1968) was used to measure plasma prolactin levels after the i.m. or i.v. injection of acepromazine in eight sheep of the Clun Forest breed (Table 1). Evidence for the specificity of the plasma prolactin measurements has been adduced (Bryant & Greenwood, 1968). Nevertheless prolactin concentration in plasma has been expressed in terms of the weight of the reference standard preparation (NIH-P-S 6). If biological and immunological measurements were identical, the levels of plasma prolactin of 50–500 ng./ml. obtained here would be equivalent to 1·25–12·5 m-u./ml.
The four female sheep investigated formed part of a study relating the degree of parasitic infestation with the reproductive cycle (Connan, 1968), and
