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Pituitary responses to luteinizing-hormone-releasing-hormone (LRH) in the postpartum periods were studied. Following a subcutaneous injection of 100 μg of synthetic LRH to postpartum subjects, no statistically significant changes in the levels of LH and FSH could be demonstrated in five subjects on postpartum day 1 or 3 and in three subjects on postpartum day 8. A normal elevation of LH and FSH following LRH was demonstrated in one subject 36 days post partum. The findings are in agreement with previous studies demonstrating a persistence of pituitary suppression during the early postpartum period. No correlation could be drawn between the pituitary responses to LRH and the plasma levels of estradiol-17β and progesterone.

Mean plasma prolactin levels obtained from male rats following anesthesia with ketamine, decapitation or via indwelling venous catheters were not significantly different although a larger variance was found in the samples obtained via catheters. Ketamine, at anesthetic doses, did not affect the increases in prolactin produced by reserpine or α-methylparatyrosine. Ketamine, at various doses, did not potentiate the effect of subthreshold doses of 5-hydroxytryptophan on prolactin secretion. Thus, ketamine would appear to be a suitable anesthetic for use in studies of prolactin secretion in male rats. Further studies in female rats are required.Supported in part by grant nos. USPHS MH 30938, 29206, and RCSA MH 47808 to HYM.

Buspirone, an effective antianxiety compound, produced a dose-dependent, relatively prolonged increase in rat plasma prolactin (PRL) levels. The stimulation of PRL secretion by buspirone was additive with the effect of a-methyl-p-tyrosine (AMPT) or ?-butyrolactone. In vitro, buspirone itself had no effect on the release of PRL from rat pituitary glands but it blocked the inhibitory action of dopamine (DA). Buspirone also increased DA turnover in the striatum as measured by the AMPT-induced depletion of striatal DA levels. These results demonstrate the ability of buspirone to block pituitary and striatal DA receptors.

Although d- and l-amphetamine had no effect on plasma prolactin levels in untreated male rats, both d- and l-amphetamine reversed the increase in plasma prolactin levels produced by reserpine and 5-hydroxytryptophan (5-HTP). Only d-amphetamine significantly reversed the effect of alpha-methylparatyrosine (AMPT) on plasma prolactin levels. This reversal is probably due to a direct or indirect dopamine agonist effect of amphetamine, rather than to an effect on norepinephrine. This conclusion is based on the finding that apomorphine, a direct-acting dopamine agonist, reversed the reserpine-induced increase in prolactin secretion, while clonidine, a direct-acting alpha-adrenergic agonist, potentiated the reserpine-induced stimulation of prolactin secretion. The effect of d-amphetamine on the increase in plasma prolactin levels produced by reserpine, 5-HTP, or AMPT was always greater than that of the l-isomer, suggesting that the d-isomer has a more profound effect on dopaminerelease or neuronal reuptake, or both, than l-amphetamine. Chronic administration of d-amphetamine prior to reserpine did not inhibit the ability of d-amphetamine to reverse the reserpine-induced increase in plasma prolactin. Chronic administration of AMPT did not enhance the ability of d-amphetamine to reverse the AMPT-induced increase in plasma prolactin.

Summary Fluoxetine (Lilly 110140) is a potent, specific serotonin (5-HT) uptake blocker which is being tested in man for antidepressant activity. One of 9 depressed patients receiving this drug developed a dystonic reaction, parkinsonian rigidity, and increased serum prolactin levels, all signs of decreased dopaminergic activity. Homovanillic acid levels also decreased in the cerebrospinal fluid of this subject. We postulate that fluoxetine, via the increase in 5-HT activity resulting from 5-HT uptake blockade, inhibited both the nigro-striatal and tubero-infundibular dopaminergic neurons. These results provide additional evidence for a linkage between serotonergic and dopaminergic neurons in man.

We report the establishment of a new cell line, designated Fang-8, which originated from a human adrenal adenocarcinoma. It has been continuously propagated during the past 20 months. The cells exhibit an epithelioid morphology, resembling the cell structure of the zona reticularis when viewed by electron microscopy. Since passage 12, the cells showed a characteristic ring-forming property in culture. The cells produce neither testosterone, mineralocorticosteroids, nor glucocorticosteroids; instead, they possess the unique function of estrogen production. Karyotypic analysis revealed a 100% aneuploid, unstable karyotype in the hyperdiploid stem line. Identification of the Y chromosome was uncertain. In view of these characteristics, Fang-8 represents a new human cell line, unlikely to be contaminated with HeLa strains, and different from another cell line derived from human adrenal cortex andenocarcinoma, namely SW-13(ATCC CCL 105).

Perlapine is a dibenzohetereopine compound chemically related to clothiapine, loxapine, and clozapine. Although the latter three compounds are antipsychotic, perlapine has not been reported to be antipsychotic. Nevertheless, all four drugs increase rat plasma prolactin levels. The order of potency is loxapine, perlapine, clothiapine, and clozapine. These results suggest that either perlapine should be reexamined for antipsychotic properties or there are hitherto unsuspected discrepancies between the dopamine receptors relevant to antipsychotic activity in man and those that regulate prolactin secretion in the rat.

Department of Medicine, The University of Chicago, Chicago, Illinois 60637, U.S.A.(Received31 May1978)Zinc deficiency in childhood may result in retardation of growth and hypogonadism, since affected adolescent boys show increased growth and sexual maturation after zinc replacement therapy (Sandstead, Prasad, Schulert, Farid, Miale, Bassilly & Darby, 1967; Halsted, Ronaghy, Abadi, Haghshenass, Amirhakemi, Barakat & Reinhold, 1972). Testicular dysfunction has been found after zinc deficiency due to chronic haemodialysis for uraemia and can be reversed by zinc supplements (Antoniou, Shalhoub, Sudhakar & Smith, 1977). Furthermore, oligospermic men, after treatment with zinc, showed increased plasma concentrations of androgens and raised sperm counts (Hartoma, Nahoul & Netter, 1977). The present study investigated the preventative effects of zinc on rats treated with dl-6-(N-α-pipecolinomethyl)-5-hydroxyindane maleate (PMHI), a potent and specific antitesticular agent whose mechanism of action has yet to be determined (Boris, DeMartino & Trmal, 1974).Three groups of 28-day-old male Sprague–Dawley

Department of Medicine, The University of Chicago, Chicago, Illinois 60637, U.S.A.(Received14 February1977)Metoclopramide is a potent stimulator of prolactin release in man (Delitala, Masala, Alagna & Devilla, 1975; Judd, Lazarus & Smythe, 1976; McCallum, Sowers, Hershman & Sturdevant, 1976); its possible effect on other anterior pituitary hormones is not known. We have carried out two experiments with male Sprague-Dawley rats, 130–150 g in weight; the results presented here demonstrate that metoclopramide specifically stimulates the release of prolactin.Groups of five rats were injected s.c. with 0·9% saline (5 ml/kg body wt) containing 0-10 mg metoclopramide/kg (supplied by A. H. Robins Co., Richmond, Virginia). Thirteen minutes later the rats were immobilized with ketamine (supplied by Bristol Laboratories, Syracuse, New York), 100 mg/kg, i.p.; ketamine does not affect the level of prolactin in the plasma of rats (Lawson & Gala, 1974). Blood was drawn by heart puncture within 2

University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637, U.S.A.(Received18 July1975)The biochemical basis of the genetically determined difference in sexual hair growth between oriental and caucasian men has not been established. Oriental men have plasma testosterone levels equal to those of Occidentals. However, the former group has low 17-oxosteroid excretion and beard growth can be induced by androgen, findings compatible with hypoandrogenism (Kobayashi, Lobotsky & Lloyd, 1966). Available data do not exclude differences in plasma testosterone binding or levels of other androgens. Therefore, the following studies were undertaken.Six, 24 ± 0·81 (S.D.) -year-old normal graduate students of oriental descent (3 Chinese, 3 Japanese) who were unable to grow beard, moustache, or sideburns were compared with six, 24 ± 4·6-year-old, Caucasian graduate students who were fully virile. Hormone levels were measured in single, fasting, 08.00 h blood specimens.Plasma testosterone, androstenedione, dihydrotestosterone, and dehydroepiandrosterone (DHA) were

Studies have been made of the effects of chronic, physiologic estradiol (E2) therapy on skeletal growth and evolution of mature hypothalamic-pituitary regulation of gonadotropin release, as well as sexual development. The response to 1-2 mg/month depot E2 im for 1-1 1/2 yrs was studied in 7 cases of Turner's syndrome and 1 with multiple endocrine deficiencies with average age 16 yrs., LH 278 and FSH 1582 ng/ml.Doses of 1.5-2 mg E2 uniformly induced breast development and menarche. Sexual hair progressed in all patients, independently of the onset of adrenarche. The growth rate doubled to 1.4 in./yr. The average growth rate per year advancement of skeletal age was unchanged by E2 therapy.Before therapy the height and suppressibility of the gonadotropin level were independent of age. When E2 was withheld after 1 yr therapy, LH and FSH were similar to before. However, subsequent E2 injection did not inhibit LH as much as before (p< .01), although depression of FSH was comparable.Conclusions: 1) These studies indicate that physiologic doses of E2 do not deleteriously affect epiphyseal fusion and growth potential. Therefore, this appears to be an optimal therapeutic regimen. 2) These studies demonstrate for the first time that an early event in puberty is reduced sensitivity to E2 of the specific negative feedback mechanism controlling LH release. Furthermore, this change in the hypothalamic-pituitary axis seems to be induced by E2.

University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637, U.S.A.(Received28 October1974)The relation of androgen production to oestrogen and gonadotrophin production and ovarian fine structure has been examined in rats in constant oestrus (CO) induced by exposure to constant light (CL).Two groups of 60-day-old virgin Sprague-Dawley rats were studied 4 months apart. Group 1 was exposed to 12 h light: 12 h darkness, Group 2 to 14 h light: 10 h darkness for 25 days, then half of each group was moved to constant light; from this time the animals were handled daily. Daily vaginal smears were performed after 110 days. Normal rats had three consecutive normal oestrous cycles, CO rats had 2–5 weeks of persistent vaginal cornification without leucocytes. Normal and CO rats were studied simultaneously at 160–175 days, between 09.00 and 11.00 h. Under ether anaesthesia, blood was removed by cardiac puncture and