Abstract
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.
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