Characteristics of the effect of estradiol on prolactin secretion by adenohyophyseal cells from intact and ovariectomized rats in primary monolayer cultures]

Estradiol directly stimulated the secretion of prolactin by the adenohypophyseal cells of intact rats in a monolayer culture. Complex interactions between estradiol and some other regulators of the hypophyseal lactotropic function were revealed. It was established that changes in prolactin synthesis and secretion in ovariectomized rats persisted for 3--4 days of adenohypophyseal cell cultivation in vitro.     

Metoclopramide potentiates the hypophyseal reactions to oestradiol

Male rats to which oestradiol benzoate was administered intramuscularly twice a week for three weeks in 1 mg doses as an aqueous microcrystal suspension showed an increase in adenohypophyseal weight, in the number of lactotropic cells in the adenohypophysis (demonstrated by immunohistochemical detection of prolactin) and in polyphenol oxidase (ceruloplasmin) activity in the blood and hypothalamus. The simultaneous administration of metoclopramide (methoxychloroprocainamide) in doses of 10 mg/rat per day in food potentiated the adenohypophyseal reaction to oestradiol (weight and the number of lactotropic cells), but potentiated the polyphenol oxidase reaction only little or not at all. Metoclopramide thus has an anti-dopaminergic effect similar to that of perphenazine and other inhibitors of dopaminergic neurones.     

Somatotropic and lactotropic receptors in transgenic mice expressing human or bovine growth hormone genes

The somatotropic and lactotropic receptors were studied in liver microsomal preparations from transgenic mice carrying the human growth hormone (hGH) or bovine growth hormone (bGH) gene fused to mouse metallothionein-I (MT) or phosphoenolpyruvate carboxykinase promoter/regulator (PEPCK). Specificity studies indicated that, similarly to normal mice, liver microsomes from the transgenic animals possess a mixed population of somatotropic and lactotropic binding sites. In transgenic animals of both sexes, the binding capacity of somatotropic receptors was significantly increased without corresponding changes in affinity. Expression of the MT-hGH hybrid gene was associated with the induction of somatotropic receptors which was approximately twice as great as that measured in animals expressing the MT-bGH hybrid gene. The binding capacity of lactotropic receptors in liver microsomes (quantitated, by the use, of labelled ovine prolactin) was increased 2–3 fold in transgenic females and approximately 10-fold in transgenic males as compared to the respective normal controls. We conclude that lifelong excess of GH up-regulates hepatic GH and prolactin receptors, and that lactogenic activity of GH is not essential for induction of prolactin receptors in the liver of transgenic mice.     

Effect of C-terminal tetrapeptide cholecystokinin (CCK-4) on the function of the islands of Langerhans and the adenohypophysis

A study was made of the action of C-terminal tetrapeptide cholecystokinin (CCK-4) on the secretory function of A-, B- and D-cells of the islets of Langerhans and on the lactotropic function of the hypophysis. Intravenous injection into rats of CCK-4 in doses of 5 and 50 micrograms/kg bw resulted within 2 min in increased blood immunoreactive insulin. Tetrapeptide also exerted a stimulant dose-dependent action on the function of insulin-, glucagon- and somatostatin-secreting pancreatic cells of the pancreatic islets in culture at concentrations ranging within 10(-9)-10(-6)M. When given in the same doses CCK-4 did not affect basal or dopamine-inhibited prolactin secretion by cultured adenohypophyseal cells. It is concluded that CCK-4 stimulates insulin, glucagon and somatostatin secretion by direct contact with target cells.     

Rate of thymidine incorporation and incidence of parenchymal cell division in adult rat hypophyseal cell cultures. Effect of thyroliberin and somatostatin

Cell suspensions derived from adult rat anterior pituitary glands were cultured for up to eight days. Prolactin immunoreactivity and/or tritiated thymidine incorporation into DNA of cell nuclei were demonstrated in cells with and without thyroliberin (TRH) and somatostatin (SRIF) treatment. It has been established that (a) TRH, which is effective in releasing both thyrotropin and prolactin, may stimulate cell proliferation in other than its target cells; that (b) SRIF has no effect on lactotropic cell proliferation and augments thymidine incorporation into DNA of unidentified cells; that (c) immunoreactive lactotropic cells with tritium-labelled nuclei are present in each culture, independent of hypothalamic hormone treatments.     

Effect of calcitonin on the prolactin surge of proestrus

The effect of calcitonin (CT) on the prolactin (PRL) surge of proestrus in rats was investigated under normal and perturbed lighting conditions. Salmon calcitonin (SCT) was injected i.p. on diestrus 2 or on proestrus, plasma PRL levels were measured by radioimmunoassay. SCT had no effect on the PRL surge under normal lighting conditions but it induced a small drop in PRL level measured on proestrus morning, 3 hours after CT injection. Animals submitted to perturbed light conditions had higher PRL levels than those kept under normal lighting. These data would indicate that for the female rats on proestrus the sensitivity to stress due to injection and blood sampling may be modulated by changing the photoperiod. SCT injection under these conditions may facilitate this destabilization in PRL level.     

Hypoprolactinemic Action of Calcitonin and the Tuberoinfundibular Dopaminergic System

Abstract: The effects of calcitonin on neurochemical parameters related to the tuberoinfundibular dopaminergic system have been investigated in an attempt to elucidate how calcitonin decreases serum prolactin levels. Intracerebroventricular human or salmon calcitonin injection decreases serum prolactin, medial basal hypothalamic dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) and hypophysial DA and increases hypophysial DOPAC. Results suggest that calcitonin may decrease prolactin secretion via the tuberoinfundibular dopaminergic system.     

Calcitonin inhibits the rise of intracellular calcium induced by thyrotropin-releasing hormone in GH3 cells

Both human and salmon calcitonins markedly inhibit the TRH-stimulated rise in intracellular [Ca2+] in GH3 cells. Calcitonin also inhibits prolactin release from these cells. Both [Ala] salmon calcitonin and salmon calcitonin (1-23) peptide amide also inhibit this rise in [Ca2+] and also inhibit TRH-stimulated prolactin release from GH3 cells as well as from primary pituitary cell cultures. It is likely that calcitonin inhibits prolactin release in the pituitary by decreasing the extent of the rise of intracellular calcium concentration. Neither an intact disulfide bond at the amino terminus nor residues 24-32 of the carboxyl terminus of salmon calcitonin are required for this inhibition.     

Serum prolactin level changes in the maternal and fetal circulation between the 28th-40th weeks of pregnancy

Serum prolactin concentration was determined in blood samples taken from the maternal cubital vein, the umbilical vein and artery between the 28th-40th weeks of pregnancy from 108 parturients, of whom 74 gave birth prematurely and 34 gave birth at term. Results indicated that during this period the prolactin level rose in the umbilical vein and artery but not in the maternal vein. Correlative analysis showed a significant positive correlation between gestational age and the serum prolactin concentration of umbilical arterial and venous blood, but no correlation was found in the case of maternal blood. During the 28th-32nd weeks the prolactin level of maternal blood was found to be higher than that of umbilical blood while during the 33rd-36th weeks and at the 40th week the prolactin level was higher in the umbilical vein and artery. No correlation was found between the prolactin concentration of maternal and umbilical blood. On the basis of these results the authors conclude that fetal prolactin concentration changes occur independently of the maternal organism and increases during the 28th-40th weeks of pregnancy.     

Neuroendocrine modulation of haloperidol-induced catalepsy

Evidence has been accumulated implicating sex hormones as possible modulators of extrapyramidal motor function. In the present study we have investigated the effects of estrogens, progesterone, testosterone, prolactin and calcitonin on behavioral parameters related to nigro-striatal dopaminergic system, such as haloperidol-induced catalepsy in male rats. It was found that 7-days estradiol benzoate treatment (5 micrograms/rat/day) significantly increases haloperidol-induced catalepsy, suggesting a possible antidopaminergic activity of estrogens. On the other hand, prolactin facilitates nigro-striatal dopaminergic transmission. Interestingly, 7 day treatment with medroxy-acetate progesterone (MAP, 5 mg/Kg, i.p.) brings about a trend to a decrease in haloperidol-induced catalepsy, while no significantly effect was observed following acute MAP administration at the same dose. So, it is tempting to speculate that chronic progestinic treatment may result in an increase in dopaminergic tonus. Testosterone, acutely administered (5mg/kg.s.c.) induces changes similar to those observed following progesterone administration. Finally, also calcitonin is able to influence haloperidol-induced catalepsy by markedly increasing it.     

Does corpus luteum function autonomously during estrous cycle in the rat? A possible involvement of LH and prolactin

This study examined the of LH and prolactin in the control of corpus luteum function during 4-day cycles in the rat. Bromocriptine (BRC) treatment was performed on proestrus or/and estrus morning that means before or after the preovulatory release of LH. This caused complete blood prolactin depression from the time of injection until diestrus 1 afternoon. This decrease in blood prolactin concentration was associated with a rise in the tonic level of LH secretion in those females which received BRC as soon as on proestrus. We first observed that injection on the morning of proestrus of doses of BRC capable of blunting prolactin secretion on proestrus afternoon did not significantly impair the preovulatory release of LH and did not prevent ovulation occurring during the following night. The life span of the corpora lutea edified from ovarian follicles rupturing before or under BRC administration did not exceed that of those formed under physiological circumstances since 4-day cycles culminating in ovulation constantly took place in all the treated animals whatever the time of BRC injection. To determine the pattern of luteal activity in the absence of prolactin secretion, we measured blood progesterone concentration from estrus until late diestrus in female rats injected with BRC on proestrus and/or estrus at 1100 h. The initiation of the function of corpus luteum on estrus and the achievement of its full activity on diestrus 1 did not appear to be affected by BRC. By contrast the level of blood progesterone declined more rapidly on the morning of diestrus 2 in BRC-treated than in control females. The capacity for autonomous progesterone secretion by corpus luteum of the cycle was discussed in the light of previous and present observations.     

Homeostatic role of calcitonin antibodies in calcium metabolism in experimental diabetes mellitus

In experimental alloxan diabetes marked hypocalcemia and hyperglycemia are observed in the blood of rats during the acute period of the disease (from 1.5 to 2 months). After 2.5-3.5 months of diabetes calcium level reaches the upper normal limit. Simultaneously, antibodies to calcitonin appear. It is quite likely that excessive calcitonin secretion, leading to hypocalcemia, decreased insulin secretion and hyperglycemia take place in the acute stage of diabetes. When diabetes persists the antibodies to calcitonin which reveal a homeostatic reaction blocking the excess of calcitonin appear. This normalizes the level of calcium in the blood and prevents the further increase in the blood sugar level.     

A case of large prolactinoma supposed to be cured by bromocriptine therapy

The authors reported a patient with a large prolactinoma (PRL 1,716 ng/ml) who was treated with bromocriptine for two years and followed up for a subsequent 36 months. After the start of the therapy, the tumor size was dramatically reduced, and finally the disappearance of the tumor was confirmed by high resolution coronal CT. The serum prolactin level and pituitary function were normalized. The tumor has not regrown and the blood prolactin level has remained normal for 36 months since the discontinuation of bromocriptine administration. This is a very rare case report on the eradicative effect of bromocriptine on such a large prolactinoma. Another characteristic of this case was that the prolactin reserve was maintained not only before the therapy but also during the early stage of the therapy.     

Prolactin in hypertensive pregnancy.

Plasma prolactin levels were measured in 68 pregnant women with hypertension at 32 weeks gestation. They were raised in pregnancies with pre-eclamptic features, most significantly in women with a rising plasma urate level. No correlation was found between the level of the untreated blood pressure and prolactin. Proteinuria did not influence prolactin levels independently of changes in the plasma urate. The differences in prolactin levels could not be ascribed to the drugs administered.     

Systemic administration of calcitonin through ocular route.

Calcitonin has been used clinically to treat hypercalcemia, Vitamin D intoxication, osteolytic bone metastases and increased skeletal remodeling in Paget's disease. In general calcitonin is given every 6 to 12 hrs intramuscularly or subcutaneously. It has been found in this study that the same results can be achieved by giving calcitonin through eyes as ophthalmic solutions. When 25 microliters of 0.05% calcitonin was given as eyedrops to New Zealand white rabbits, it did not reach the concentration achieved by i.v. administration at the same dose level. The systemic absorption of calcitonin did not reach the level achieved by i.v. administration even though the eyedrop concentrations were increased 2-fold (0.1%) to 10-fold (0.5%). When absorption enhancers such as BL-9 and Brij-78 were added to calcitonin eyedrops, however, the systemic absorption of calcitonin was enhanced markedly. BL-9 (0.5%) increased calcitonin (0.5%) absorption 16-20 fold and raised blood concentration of calcitonin above levels achieved by i.v. injection (25 microliters, 0.05%) with 0.5% calcitonin eyedrops instillation. Effects of Brij-78 (0.5%) were even more impressive. It increases calcitonin absorption 22-24 fold and raised the blood concentration of calcitonin above the levels achieved by i.v. injection (25 microliters 0.05%) with 0.15% and 0.5% calcitonin eyedrops instillation. These results indicate that the therapeutic level of calcitonin can be reached through the ocular route.     

Acute effect of large doses of calcitonin on calcium, magnesium and inorganic phosphate levels in rat serum in correlation to differences in thryroid function.

The acute effect of pharmacological doses of porcine calcitonin were studied on the calcium, inorganic phosphorus and magnesium level in correlation to thyroid function in experimental rats. In every case, and with all three doses, the serum calcium and inorganic phosphorus level fell significantly within 60 minutes after calcitonin administration. The drop in both minerals was most pronounced in the group with experimental hyperthyroidism, in which all different doses had the same effect. In experimental hypothyroidism, the decrease was correlated to the dose. In the case of the serum magnesium level, a statistically significant drop was observed in animals with hyperthyroidism after the two largest doses of calcitonin, while only a mild increase occurred in animals with hypothyroidism after the smallest dose. None of the doses of calcitonin affected the magnesium level in animals with normal thyroid function.     

The effect of calcitonin on prolactin secretion during gestation

The relationship between calcitonin (CT) and prolactin (PRL) was studied by means of the injection of salmon calcitonin (SCT) i.p. on day 1 of gestation. An estrogen inhibitor - clomiphene - was also administered to certain groups of animals on day 4 and 5 of gestation. SCT did not affect PRL levels on day 1 of gestation nor on days 5 or 7, but it prevented the rise of PRL levels observed in animals submitted to injection stress on days 4 and 5. In animals treated with clomiphene, the inhibition by SCT on PRL increase after injection stress was partially abolished. SCT while not affecting basal PRL level prevented the rise observed after stress and this effect occurred some days later. Thus SCT could exercise a delayed neuroendocrine control. This action of SCT seemed to be partially dependent upon the presence of estrogens.     

Plasma calcium and calcitonin in the marine teleost, Gadus morhua

Total, free and ionic plasma levels of calcium as well as total plasma magnesium and inorganic phosphate levels were studied in the Atlantic cod, Gadus morhua, in relation to salmon calcitonin injections. Plasma ion levels and endogenous levels of calcitonin were studied during environmentally induced hypercalcemia. It is concluded that no apparent relationship between calcitonin and calcium levels was found, and it is implied that calcitonin in fish may have a physiological function not related to blood calcium regulation.