Mammary Prolactin Research Articles

Preferential establishment of a slowly dissociable component in plasma membrane compared to intracellular prolactin receptors.

AbstractProlactin dissociates more readily from rat liver than from rabbit mammary prolactin receptors. The rate of dissociation is dependent in the time of association. In rat liver, prolactin dissociates from receptors at the cell periphery (plasma membrane, PM) more rapidly than those of microsomes, a major component of which is the intracellular Golgi membranes. The dissociation curves following 1 hr of association can be resolved into a fast and slow component by logarithmic transformation, with a greater than twofold increase in the fast componment of the dissociation rate constant (k2) in PM compared to microsomal membranes. With longer association times (10 hr), plasma membranes develop a more slowly dissociable component, with dissociation characteristics (rate constants) similar to those observed in microsomes following 1 hr of association. Another means of visualizing this difference is by a Scatchard plot of prolactin binding to PM, microsomal, and Golgi membranes. The affinity constants in th...

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.

Effects of long term exposure to beer on the genesis and development of spontaneous mammary adenocarcinoma and prolactin levels in female virgin C3H/St mice.

The exposure of female inbred virgin C3H/St mice infected with the Bittner particle to a commercial brand of beer increases body weight but has no significant effects on survival, the incidence of spontaneous mammary adenocarcinoma, tumor latency, or growth even on continuous administration of beer in place of drinking water over the entire postweaning lifespan of the animals. Prolactin excretion in young beer-group mice was slightly elevated but not significantly different from the prolactin levels observed in normally maintained control animals.

Hormone and drug effects on growth of DMBA mammary tumours and plasma prolactin levels in adreno-ovariectomized rats.

The effects of hormone and drug treatments on plasma prolactin (PRL) levels and mammary tumour growth were investigated in rats bearing continuously growing DMBA-induced mammary tumours that responded to bilateral adreno-ovariectomy (Ax + Ox), Oestrogen (E2) administration increased both plasma PRL and tumour growth, but was unable to sustain tumour growth when the PRL level was reduced by concurrent injection of ergocornine (Eg). Perphenazine (Pz) produced a dose-related increase in plasma PRL, but stimulation of tumour growth in the absence of E2 required a minimal level of plasma PRL induced by Pz (0.15 mg/100 g body wt/day or more). Progesterone (P) (3 mg/day) alone, although without effect on PRL levels, maintained static tumour growth (i.e. it had a slight stimulatory effect) irrespective of the duration of treatment. The increase in plasma PRL levels above the basal values in the Ax + Ox controls following injections of combined P + Pz (0.1 mg/100 g/day) was sufficient to sustain static tumour growth, but not to reactivate growth. Enhancement of both plasma PRL and tumour growth did not occur until P and higher doses of Pz (0.3 mg/100 g/day) were injected jointly; this treatment, however, while unable to stimulate continuous tumour growth, was able to maintain static growth when plasma PRL was reduced by concurrent injections of P + Pz + Eg. From these findings it is postulated that the mechanism of action whereby P maintains static tumour growth is different from that of PRL and independent of circulating PRL levels.

The effect of metoclopramide, TRH and L-dopa on prolactin secretion in pituitary adenoma and in "functional" galactorrhoea syndrome.

The degree of autonomy in prolactin secreting pituitary adenomas and also prolactin secretory reserve in cases with suspected functional galactorrhea syndrome was evaluated with the use of metoclopramide, TRH and L-DOPA. It was found that in patients with pituitary adenoma the basal prolactin (PRL) level often exceeded 150 micrograms/l and the response to stimulation with TRH and/or metoclopramide was markedly diminished or even nonexistent, while the response to L-DOPA was usually retained. In patients with galactorrhoea and/or amenorrhoea, with normal skull X-ray the basal PRL level was either normal or moderately raised but the response to stimulation was various; mostly it was excessive, it was sometimes normal, but in some other cases it was markedly diminished as in patients with adenoma. In the author's opinion the so-called "functional disorder" of prolactin secretion is mainly hyperresponsiveness to stimulation, whereas the basal PRL level in those cases is usually normal or only intermittently raised. In the cases with a moderate hyperprolactinaemia, especially if it appears to be constant, and the response to stimulation is diminished or none at all, we suspect a pituitary microadenoma. Finally, there are rare cases of galactorrhoea with normal basal PRL and normal response to stimulation, in which the sensitivity of the mammary PRL receptor is probably increased. We suggest therefore that the above mentioned PRL stimulation tests may help in distinguishing between tumoural and functional hyperprolactinaemia.

Rabbit mammary prolactin receptors. Demonstration of a late puerperal increase in affinity.

Crude receptor preparations of rabbit mammary gland were made by differential centrifugation and reacted with lactoperoxidase-iodinated ovine prolactin (oPRL) in order to determine their binding characteristics. Receptors prepared from the mammary glands of animals less than 4 days postpartum bound oPRL with high affinity (Ka = 3.50 X 10(9) M-1), in good agreement with previous results of other investigators. The binding capacity of these preparations was 107 +/- 16.3 fmol/mg of protein. In contrast, receptors prepared from the mammary glands of late lactating rabbits (Days 25 to 30 of lactation) showed a 2.5-fold increase in binding affinity (Ka = 8.63 X 10(9) M-1, p less than 0.001) without a significant increase in binding capacity (135 +/- 21.4 fmol/mg, p greater than 0.2). Kinetic experiments revealed that the rates of association of hormone and receptor were identical in early and late receptor preparations, and that the 2.5-fold decrease the dissociation rate observed in the late preparations was fully explanatory of the differences in equilibrium binding. The mechanism of this affinity increase is not known. Such a change in binding characteristics, which would tend to enhance tissue responsiveness, may underlie the well characterized maintenance of full lactation in women despite falling concentrations of prolactin.

Induction of mammary prolactin receptors and lactose synthesis after ovariectomy in the pregnant mouse.

The development of prolactin receptors in the mammary gland after ovariectomy was investigated in pregnant KA mice. Mice were ovariectomized on day 13 of pregnancy and used for the determination of the amount of specific binding of 125I-labelled prolactin to the mammary tissue, and the contents of lactose and nucleic acids in the mammary gland 0, 8, 24, and 72 hr after the operation. The specific binding of 125I-labelled prolactin, lactose and RNA contents in the mammary gland remained low until 8 hr, sharply increased 24 hr and decreased 72 hr after ovariectomy. When ovariectomized mice were treated with 0.2 mg progesterone, pregnancy was maintained and an increase (1.5-fold) in the amount of specific binding was observed with an increase of lactose content. Five mg progesterone completely inhibited lactose synthesis. Cortisol administered with progesterone did not show any specific change at the dose used (0.5 to 10 mg). Although the amount of specific binding was also increased after hysterectomy, this increase (2-fold) did not fully cover the increase after ovariectomy (3-fold). These results suggest that the recepter site for prolactin is induced before the initiation of lactose synthesis caused by ovariectomy during pregnancy.

Prolactin and Estrogen Binding Sites in the Mammary Gland of the Lactating and Non-Lactating Rat

Mammary glands from lactating and non-lactating post-partum rats were assayed for prolactin (PRL) and estradiol (E2) binding sites. In lactating animals serum PRL and tissue E2 and PRL binding increased rapidly in the first 2 days post-partum and thereafter declined until day 15 to 20 post-partum. In non-lactating rats in the postpartum period, no comparable changes in the three parameters were observed. Hysterectomy of pregnant rats on day 21 was followed by an increase in serum PRL concentrations but no increase in mammary tissue binding of PRL or E2 was found. Similar results were observed after hysterectomy and oophorectomy except no increase in serum PRL was noted. The administration of estradiol to the mother immediately after birth decreased mammary tissue PRL binding sites, while the administration of hydroxyprogesterone decreased binding of E2 but left PRL binding unchanged. Post-partum suppression of PRL secretion with Bromocriptin decreased PRL but not E2 binding and, in addition, decreased wei...

Prolactin receptors: characteristics of the particulate fraction binding activity.

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.

Relation between growth of carcinogen-induced mammary cancers and serum prolactin values in rats.

SummaryMammary cancers were induced in fifty 50-55 day old female Sprague-Dawley rats by a single intravenous injection of 5 mg 7,12 -dimethylbenz (a) anthracene (DM BA). Total mammary cancers and average cancer diameter per rat were measured once weekly. Beginning about 45 days after the appearance of mammary cancers and approximately at monthly intervals thereafter, for a total of 165 days, serum prolactin was measured by radioimmunoassay. Although the average number of mammary cancers increased from an initial 1.5 ± 0.5 to a maximum of 7.4 ± 0.9 per rat, and average tumor diameter increased from 0.7 ± 0.1 to 1.4 ± 0.2 cm, serum prolactin concentrations remained within the normal range and did not change significantly from month to month. These observations indicate that growth of DMBA-induced mammary cancers in Sprague-Dawley rats can proceed in the presence of normal blood prolactin values.

Relationship among nursing frequency, lactation pituitary prolactin, and adrenocorticotropic hormone content in rats.

SummaryIncreasing the nursing frequency in rats from non-nursed levels (controls) to Ix, 2x, 4x and ad libitum frequencies progressively increased mammary DNA, RNA and pituitary prolactin content 4.3-, 21.1-and 2.1-fold, respectively. Pituitary ACTH content, although always detectable, was unaffected by nursing frequency.

Effects of cortisone, hydrocortisone and ACTH on mammary growth and pituitary prolactin content of rats.

Summary1. Physiological saline (0.85%) or 2 mg doses of ACTH, cortisone or hydrocortisone were injected daily for 10 days into 42 intact, mature female rats. All 3 hormones elicited branching of ducts, lobule-alveolar development and secretory activity in mammary glands. This was most marked for cortisone and least for ACTH at the dose levels employed. 2. Cortisone increased pituitary prolactin content by about 23%, hydrocortisone by about 41% and ACTH by about 71%. 3. It is concluded that these hormones can initiate mammary development and secretion in the intact rat, but that further work is needed to establish their normal role in these processes.