SUMMARY Treatment for 5 days of female rats with perphenazine (5 mg/kg/day) induced full lobulo—alveolar differentiation. Long-standing adrenalectomy (12 days) decreased this mammotrophic effect of perphenazine. The mechanism of this reaction was studied in male rats in order to avoid fluctuations of the prolactin content in the anterior pituitary. Adult male rats were adrenalectomized and injected s.c. after 12 days with perphenazine (10 mg/kg). Two hours later the rats were killed and pituitary and serum prolactin levels assayed by double antibody radioimmunoassay. In intact rats, perphenazine treatment enhanced serum prolactin up to 104 ± 4 ( s.e.m. ) ng/ml (± 350%). Adrenalectomy alone increased serum prolactin from 30± 5 to 47 ± 6 ng/ml (+56%), and augmented the perphenazine-induced release of prolactin from the pituitary into the blood from 104 ± 4 to 147 ± 10 ng/ml (+ 42%). In chronically adrenalectomized adult female rats extremely high amounts of prolactin (+ 1617%) were detected in the serum at the end of 5 days' treatment with perphenazine (5 mg/kg/day). These results indicate that removal of the adrenals in male and female rats does not interfere with the ability of the pituitary to secrete prolactin. Moreover, they also show that in adrenalectomized rats the impaired mammotrophic effect of perphenazine is not due to prolactin deficiency (since high serum levels of this hormone were present) but to the absence of corticosteroids at the target organ.

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.

Hot dry winds (Sharav in Israel) are notorious for causing controversial symptoms such as depression, discomfort, headaches, irritability and exacerbation of respiratory ailments. Daily urinalysis combined with study of the complaints of two hundred weather-sensitive patients suffering from Sharav have shown that there exist at least three different patterns of reaction: serotonin hypersecretion causing a general "Irritation Syndrome", catecholamine deficiency resulting in the "Exhaustion Syndrome", histamine and creatinine overproduction combined with clinical "Hyperthyroidism - Forme Fruste" and typical thyroid complaints. These syndromes are amenable to appropriate treatment controlled by urinalysis.

SUMMARY Treatment of intact or recently (1 day) ovariectomized female rats with 5 mg perphenazine (Trilafon)/kg/day for 5 days resulted in marked lobulo—alveolar differentiation of the mammary glands. Perphenazine failed to stimulate mammogenesis in chronically (12 days) ovariectomized rats, unless they had been primed with oestradiol. However, mammogenic effects in chronically ovariectomized rats were obtained after implantation of minute amounts (2 μg) of oestradiol into the median eminence, or after treatment for 16 days with the non-steroid pituitary gonadotrophin-inhibitor methallibure (ICI 33828; 20 mg/kg/day). Since these latter procedures counteract the gonadotrophin surge after ovariectomy, it would appear that inhibition of gonadotrophin secretion is necessary before prolactin secretion can be stimulated by perphenazine. Castrated male rats responded to perphenazine with lobulo—alveolar differentiation similar to that in intact males. The implications of this difference with regard to the mechanism of pituitary response to gonadectomy are discussed.

The acute effects of a single injection of perphenazine on pituitary and blood prolactin levels were studied in male rats and rabbits. Prolactin from both sources was determined by bioassay. A significant rise in blood prolactin became visible as early as 0.5 h after injection of perphenazine – earlier times were not studied – and remained high for at least 4 h. The prolactin peak following intravenous injection in rabbits was attained after 1 h, while in rats injected sub-cutaneously, it was reached after 2 h. Concomitantly, pituitary prolactin in rats decreased, falling to a minimum level within 2 h, and remaining low for at least 4 h. These results are interpreted as further evidence that perphenazine induces immediate release of prolactin from the pituitary into the blood. This release is probably due to suppression of the hypothalamic prolactin-inhibiting factor. The possibility that perphenazine promotes prolactin synthesis is also discussed.

SummaryThe F metabolism was compared in pregnant and non-pregnant rats of 170 g weight. In the bones, F content was similar in both groups, and when F supply exceeded 14.55 ppm, there was a pronounced increase in bone F content. In fetal bones, the increase appeared at lower levels of supply, i.e. 5.2-14.55 ppm. In the blood, F levels were similar in pregnant and non-pregnant rats. At intakes exceeding 14.55 ppm, there was only a slight increase in blood F in both groups. In the urine, F levels increased in both groups similarly, and rather steeply with increased F intake, thus indicating immediate removal of any F surplus with the urine in pregnant and non-pregnant rats. It is stressed that this metabolism is different from that observed in pregnant women, who tend to retain an F surplus-during pregnancy.