M. Ben-David

SERUM-PROLACTIN IN WOMEN WITI PREMENSTRUAL SYNDROME

Abstract Serum-prolactin was measured by radioimmunoassay during the menstrual cycle in 28 women who had the premenstrual syndrome (P.M.S.) and in a control group who did not have P.M.S. symptoms. Throughout the menstrual cycle mean serum-prolactin was significantly higher in women with P.M.S. than in the controls. The average individual increase in serum-prolactin during the premenstrual period compared with the first 3 weeks of the cycle was also significantly higher in women with P.M.S. It is not clear whether the increase in serum-prolactin was merely an indicator of stress or was actually involved in producing some of the symptoms which constitute P.M.S.

Anti-hypercholesterolemic effect of dehydroepiandrosterone in rats.

Summary Dehydroepiandrosterone (DHA) and 3α-methoxy − 17α−methyl− 5α −androstane−17α−01 (SC-12790) were studied for their anti-hypercholesterolemic and thyromimetic activities. The following findings were established: 1. DHA (5 mg/kg/d per os for 10 days) was found to be an anti-hypercholesterolemic agent which prevented increase in the serum cholesterol level (SCL) of rats made hypercholesterolemic by propylthiouracil (PTU) treatment. It was also found that the same dose of DHA given over a period of 21 days prevented an increase in SCL in rats made hypercholesterolemic by combined PTU and cholesterol feeding. DHA, however, did not reduce the SCL of normal rats. 2. SC-12790, when given under the same experimental conditions as DHA, did not reduce the SCL of hypercholesterolemic rats. 3. DHA did not produce any change in thyroid weight as did exogenous TSH and T-3. It seems that the anti-hypercholesterolemic effect of DHA cannot be explained by a thyromimetic activity. These findings are of clinical importance since DHA, which is a weak endogenous androgen, is orally active as an anti-hypercholesterolemic agent. The possible mechanism of its action is discussed.

Suppression of prolactin secretion by acute administration of delta9-THC in rats.

Summary The effect of acute administration of δ9-THC, an active principle of marihuana, on serum prolactin was studied in normal, adult, unanesthesized male rats. Animals were ip injected with doses ranging between 0.5 and 10 mg/kg and killed after periods of 15–240 min. Serum prolactin was measured by a radioimmunoassay. Delta-9-THC (5 mg/kg) significantly lowered serum prolactin to 37% of control values within 30 min. This effect, however, was terminated after 4 hr. As reported earlier, perphenazine treatment resulted in a profound increase (350%) in serum prolactin. This effect, however, was not counteracted by addition of δ9-THC. The mechanism by which δ9-THC suppresses prolactin release is yet unknown.

EFFECT OF DIFFERENT STEROIDS ON PROLACTIN SECRETION IN PITUITARY-HYPOTHALAMUS ORGAN CO-CULTURE.

Summary Various steroids were added to pituitary culture or pituitary-hypothalamus co-culture in vitro, and their effect on pro-lactin release was studied. 1. Estradiol and hydrocortisone are strong stimulants of pro-lactin release, apparently acting directly through the pituitary. 2. 3-Alpha-hydroxy-11, 20-diketo-pregnane-3-hemisuccinate and, to a lesser degree, progesterone are depressants of prolactin release, acting directly on the hypophysis. 3. Testosterone does not affect prolactin release from the pituitary. Estradiol, 3-alpha-hydroxy-11, 20-diketo-preg-nane-3-hemisuccinate = Meket, testosterone, hydro-cortisone and progesterone were generously supplied by Dr. G. A. Overbeek of Organon-Oss, Holland, and perphenazine (Perphenan) by “Taro,” Pharmaceutical Ind., Haifa, Israel.

Production of Lactation by Non-Sedative Phenothiazine Derivatives.

According to recent observations, the hy-pothalamus contains a prolactin-inhibiting factor (P.I.F.) (1,2,3), which has been shown both in vitro and in vivo. In vitro the hy-pophysis-hypothalamus organ co-culture technique (1,2,4,5) has proved that presence of the hypothalamus inhibits prolactin secretion from the hypophysis. In vivo, however, mammary gland development and lactation can be achieved by: (a) hypothalamic lesions in rats and rabbits(6,7), (b) cutting of the pituitary stalk in women (8) and goats (9), (c) hypophyseal autografts in rats (10) and mice (11) at sites not controlled by the hypothalamus, (d) treatment with hypothalamus-de-pressing tranquilizers(12,13,14,15,16). It is obvious from the foregoing that increased secretion of prolactin can be obtained either by interruption of the normal connection between pituitary and hypothalamus which frees the pituitary from the inhibitory influence of the hypothalamus, or by the paradoxical effect of depressing the P.I.F. The present study was carried out in order to establish which chemical configuration at the phenothiazine molecule is required to obtain specific depression of the P.I.F. and thus maximal stimulation of lactation. We also sought to find out whether any correlation exists between the tranquilizing and mammotropic effects of an effective lactational agent. Finally, the aim of this study was to find phenothiazine derivatives without tranquilizing action but possessing highest mammotropic activity. Methods. Experiments were carried out in 300 primed adult female albino rats of the Hebrew University “Sabra” strain, weighing 200 (± 10) g each. For priming, the animals Received daily s.c. 8μg estradiol in olive oil for 10 days. From the 11th day, for 5 days, i.e., up to the 15th day, the drug to be tested was injected. Twenty-four hours after the last treatment (on the 16th day), all animals were sacrificed and their right inguinal mammary pad removed.

Hyperprolactinemia: A Possible Cause of Sexual Impotence in Male Patients Undergoing Chronic Hemodialysis

Hyperprolactinemia is known to cause impotence in patients with normal renal function and elevated serum prolactin levels (SPLs) have also been reported in uremia. This study was undertaken to examine a possible role of elevated SPLs in the impotence of male patients undergoing chronic hemodialysis (CHD). SPLs in 16 male patients undergoing CHD were evaluated using a homologous double-antibody radioimmunoassay with prolactin isohormones isolated from human amniotic fluid. Patients were divided in 2 groups: 6 patients were sexually impotent and 10 sexually potent. Patients with emotional disturbances or marital conflicts known to cause impotence were excluded from the study. The SPLs of the impotent patients were found to be significantly elevated in comparison to the levels of the potent patients (136.7 +/- 28.2 vs. 37.3 +/- 2.7 ng/ml, p less than 0.001). Furthermore, in 2 patients who were successfully treated with bromocriptine to suppress hyperprolactinemia, recovery of sexual potency was noted. Thus, sexual impotence in male CHD patients seems to be associated with marked hyperprolactinemia. It is suggested that elevated SPLs may be an important cause of impotence among CHD patients.

Prolactin secretion during and after Noveril infusions to depressive patients

Dibenzapine (720 mg, Noveril) was infused intravenously to 16 depressed patients during a period of 3 h. Serum prolactin levels were determined by radioimmunoassay and changes in clinical condition were evaluated according to the Hamilton Equation. The two variables were correlated to each other. In most of the patients Noveril caused a dramatic but short-lived improvement in depressive symptoms. There was much variability in the prolactin response to the drug. Serum prolactin levels showed a great elevation in 9 patients. In all patients the hormonal levels returned to their former normal levels after termination of the infusions. The treatment was then continued with Noveril per os. There was no significant correlation between serum prolactin levels and clinical condition or its change. The elevation of serum prolactin levels as a reaction to Noveril treatment may be explained by the prominent serotonergic action of Noveril. A time lag between serotonergic and dopaminergic actions of the drug when given in higher doses may be an additional explanation. Other possible hypotheses are discussed.

Sulpiride-induced hyperprolactinemia and impotence in male psychiatric outpatients

The relationship between erectile dysfunction and sulpiride stimulatory effect on prolactin secretion was studied in 13 married male psychiatric outpatients. The patients population was comprised of 2 groups: patients with anxiety disorders resistant to minor tranquilizers who were treated with sulpiride up to 200 mg/day, and schizophrenic patients treated with sulpiride 600 mg/day. All the patients were maintained on maximal dose for a period of 3 weeks. Sexual function and blood prolactin levels were monitored once weekly. The patients who developed impotence were maintained on higher doses of sulpiride and exhibited higher prolactin levels in comparison to the potent patients. Restoration of potency was observed after reduction or discontinuation of sulpiride treatment. It is concluded that sulpiride induced impotence is associated with hyperprolactinemia.

A Sensitive in vitro Method for Prolactin Determination.

Summary The mid-part of the inguinal mammary gland of non-primed virgin, me-testric albino rats, weighing 270 ± 10 g, is sensitive to 0.001 I.U./ml of prolactin when cultivated in enriched synthetic medium M-199 for a period of 2 days. This method may replace the standard crop-gland method for prolactin assay and other routine tests for prolactin, because of its reproducibility, high accuracy and specificity. Its quantitative aspects are being worked out.

Effect of different steroids on lactating rats.

Summary The effect of different doses of estradiol, progesterone, testosterone and dehydroepiandrosterone on milk yield of normal lactating rats was assayed by daily s.c. injections of the steroids from day 7 to day 20 postpartum. It was found that high doses of estradiol (0.01–0.3 mg/kg/d) decrease milk secretion while a small dose of 0.001 mg/kg/d slightly increases it. Interruption of estradiol treatment on day 16 reestablished increased milk yield on day 20. Progesterone showed no significant decrease in milk yield at a dose of up to 100 mg/kg/d. Testosterone, and to a lesser degree dehydroepiandrosterone, were found to be potent inhibitors of milk secretion at a dose of 1 mg/kg/d while a low dose of 0.1 mg/kg/d failed to suppress milk production. The target organs of the above steroids are discussed.