Search Results

ABSTRACT

The effect of ovine prolactin on intestinal Ca absorption and placental Ca transfer was studied in pregnant ewes. Six groups of five animals bearing a single fetus were used and injected s.c. daily between days 121 and 135. The first group was given 0·1 μg ovine prolactin/kg body wt per day, the second 0·1 μg ovine prolactin/kg body wt per day plus 0·1 μg 1α-hydroxycholecalciferol (1α-OH-D₃)/kg body wt per day, the third 0 ·1 μg ovine prolactin/kg body wt per day plus 0·20 units calcitonin/kg body wt per day, the fourth 2 μg bromocriptine/kg body wt per day, the fifth 2 μg bromocriptine/kg body wt per day plus 0·1 μg ovine prolactin/kg body wt per day, and the sixth were controls injected with vehicle alone. The intestinal Ca absorption was measured on a duodenal loop tied off in vivo on day 136 and placental Ca transfer was evaluated between days 129 and 136. Ovine prolactin stimulated both intestinal Ca absorption and placental Ca transfer; these effects were further increased by 1α-OH-D₃. Calcitonin had no effect on ovine prolactin-stimulated intestinal Ca absorption, but blunted the influence of ovine prolactin on Ca placental transfer. Bromocriptine decreased both intestinal Ca absorption and Ca placental transfer but these effects of bromocriptine were overcome by simultaneous injection of ovine prolactin.

J. Endocr. (1985) 107, 171–175

SUMMARY

To determine whether human decidua and/or chorion synthesizes and secretes prolactin, explants of decidua obtained at Caesarian section and explants of chorion from the membranes separating dizygotic twins were cultured for periods of up to 6 days. The decidual explants released 366 ± 37 ng prolactin/100 mg tissue (mean ± s.d.) during each day in culture and incorporated ³H-labelled amino acids into immunoprecipitable prolactin. In the radioimmunoassay for prolactin, serial dilutions of incubation medium displaced ¹²⁵I-labelled prolactin parallel to the displacement by pituitary prolactin and the prolactin in the medium eluted from Sephadex G-150 in a position identical to that of pituitary prolactin. Chorionic explants released prolactin into the incubation medium during day 1 of culture only and did not incorporate ³H-labelled amino acids into prolactin. These results demonstrate that prolactin is synthesized by the decidua and not by the chorion and suggest that the decidua is the source of prolactin in amniotic fluid.

Hyperprolactinaemia in patients with chronic renal disease undergoing dialysis has prompted the investigation of the relative roles of liver and kidney in the degradation of prolactin. Male rabbits were acutely nephrectomized, and compared with intact animals with or without prolactin infusion. Prolactin degradation was followed after intravenous injection of ¹²⁵I-labelled ovine prolactin. Measurements were made of peptide-bound ¹²⁵I and ¹²⁵I-labelled degradation products in plasma, liver, kidney, bile, urine and muscle and total thyroid radioactivity. A significant (P<0·01) reduction in the metabolic clearance rate of ¹²⁵I-labelled prolactin was observed due to nephrectomy, with double the accumulation of ¹²⁵I-labelled peptides in the livers in this group. Prolactin infusion of nephrectomized animals had a further and larger effect than nephrectomy alone on prolactin degradation. Metabolic clearance rate significantly (P<0·01) decreased from 5·5 ml/min per kg in nephrectomized rabbits to 0·8 ml/min per kg with prolactin infusion. The accumulation of ¹²⁵I-labelled prolactin degradation products in the blood was significantly (P<0·01) lower in this group of animals and the amount of peptide-bound ¹²⁵I in plasma at 60 min after ¹²⁵I-labelled prolactin administration was significantly (P<0·01) higher. Liver degradation of prolactin in the absence of exogenous hormone appears to be sufficient to maintain an approximately normal half-life for prolactin in plasma (intact t _½ = 6·8 min; nephrectomized t _½ = 8·5 min). However, with prolactin infusion the half-life of ¹²⁵I-labelled prolactin increased to 28·5 min, and the plasma prolactin concentrations measured by radioimmunoassay rose linearly with time. These data supported the view that hyperprolactinaemia associated with renal dysfunction is substantially due to hormone oversecretion.

SUMMARY

The effect of sulpiride, a neuroleptic agent, on the secretion of prolactin by the anterior pituitary gland of the rat was studied. A significant increase in serum prolactin was observed after subcutaneous administration of the drug. Although sulpiride (0·10μmol/l or 0·14 mmol/l) had no effect on the secretion of newly synthesized or radioimmunoassayable prolactin in vitro, the drug significantly overcame the inhibitory action that dopamine (0·50 μmol/l) exerted on prolactin secretion. Rats implanted with a prolactin-secreting pituitary tumour MtTW15 showed an inhibition of prolactin biosynthesis and release. Injection of these rats with sulpiride restored prolactin biosynthesis and release of the hormone toward normal levels. These results demonstrate that sulpiride has a direct effect on the pituitary antagonizing the inhibitory effects exerted by dopaminergic mechanisms, although the drug itself does not stimulate the secretion of prolactin in vitro. Sulpiride may have a direct action on the pituitary lactotrophs in vivo, but effects at higher centres have not been excluded.

Production of prolactin is very tissue-specific – the gene is present in all cells, but in the rat it is expressed only in the anterior pituitary gland, while in man it is also expressed at low levels in the decidualized endometrium. Much of the work on rat prolactin gene expression has been greatly facilitated by the availability of the rat pituitary tumour-derived GH cell line (including the GH₁, GH₃ and GH₄ cell subclones) which produces both prolactin and growth hormone. In contrast, much less is so far known about the regulation of the human prolactin gene, due in part to the lack of readily available human pituitary tissue for in-vitro studies.

An increasing amount is known about hormonal and intracellular regulation of prolactin mRNA production, which has been reviewed elsewhere (Davis, Belayew & Sheppard, 1989). However, some of the most impressive and important recent advances have been

Department of Anatomy, Duke University Medical Center, Durham, North Carolina 27710, U.S.A.

(Received 15 July 1975)

Radioimmunoassay of luteinizing hormone (LH) in sequential blood samples collected continuously over 2–12 min periods from ovariectomized (OVX) rats has shown the concentration of LH in blood to fluctuate at high levels in a pulsatile rhythm (Gay & Sheth, 1972). The present study investigates whether plasma prolactin fluctuates regularly at low levels in OVX rats.

Sprague–Dawley rats kept in a room with the lights on from 05.00 to 19.00 h were ovariectomized and used 12–16 weeks later. A cannula was inserted into the right atrium (Terkel, 1972) before 10.00 h. At this time or 3 days later rats were placed in separate buckets containing food and water. Blood (0·3 ml) was withdrawn through the cannulae and replaced with heparinized saline over a 60 s period at 10 min intervals from 17.00 to 18.00 h

SUMMARY

Both oestradiol and perphenazine induced a significant increase in prolactin release by ovariectomized rats. Ergocornine completely inhibited the initial perphenazine-induced prolactin release which normally reaches a maximum during the first 2·5 h. However, ergocornine did not prevent a significant increase in prolactin release after daily administration of perphenazine. It inhibited oestrogen-induced prolactin release. The results support earlier suggestions that prolactin release is controlled by two mechanisms. Only one of the mechanisms can be blocked by ergocornine.

The capacity of the pigeon pituitary gland to release prolactin was investigated in vivo, to evaluate its hypothalamic regulation and to establish the dominant hypothalamic factor for prolactin secretion. After 3 days of systemic administration of some physiological and pharmacological agents, followed by 2 consecutive days of local intradermal injections of prolactin into their crop sacs, the crop mucosa was scraped, dried and weighed. The substances tested were: oestradiol and tamoxifen (antioestrogen), thyrotrophin-releasing hormone (TRH) and anti-TRH serum, perphenazine (releases prolactin in mammals) and bromocriptine (suppresses prolactin in mammals). Prolactin and anti-prolactin serum were tested as controls.

While prolactin markedly proliferated and anti-prolactin serum significantly inhibited the mucosal weight, oestradiol, TRH and perphenazine dramatically depressed proliferation of the mucosa, suggesting that prolactin secretion was inhibited. Tamoxifen, anti-TRH serum and bromocriptine significantly increased the proliferation of the crop mucosa, indicating an increase in the endogenous release of prolactin. Since the effect of these substances on prolactin release in the pigeon is the opposite from their well-established effects in mammals, these results suggest, in a specific and homologous model, that the dominating regulator for prolactin in the pigeon is contrary to that in the mammal, namely prolactin-releasing factor, and that TRH may play a significant role in the physiological regulation of prolactin secretion.