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A. K. SLOB
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M. P. OOMS
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J. T. M. VREEBURG
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Plasma levels of testosterone and LH were estimated in female and male rats at gestational ages of 19, 20 and 21 days and at 1, 3, 6, 12, 18 and 24 h after birth. Concentrations of testosterone in the gonads were also estimated in 20-day-old fetuses and at various times after birth.

Before birth female fetuses had significantly lower levels of testosterone and higher levels of LH than had male fetuses. During the first 24 h after birth female rats also had lower levels of testosterone and higher levels of LH than male rats. The pattern of levels of testosterone in the hours after birth was significantly different between female and male rats in that high levels were observed 1 and 3 h after birth in male rats (3·0 and 2·2 ng/ml respectively). This finding, as well as the relatively high levels of testosterone in female fetuses (about 50% of the levels found in male womb-mates) is discussed.

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A. K. SLOB
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M. P. OOMS
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J. T. M. VREEBURG
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Department of Endocrinology, Growth and Reproduction, Faculty of Medicine, Erasmus University, P.O. Box 1738, Rotterdam, The Netherlands

(Received 14 June 1978)

Prenatal morphological and behavioural masculinization of female foetuses through exposure to androgen from the testes of male foetuses was first suggested by Clemens (1974). It was reported that female foetuses next to male foetuses in the uterus had a larger ano-genital distance at birth and displayed more (but not statistically significant) mounting behaviour in response to administration of testosterone in adult life than did female foetuses that had not been in such close proximity to foetal male rats. More recently, Gandelman, vom Saal & Reinisch (1977) also reported that in mice, the positions of the female foetuses in the uterus relative to the male foetuses determined the extent to which the female rat was masculinized in terms of both morphology (ano-genital distance at birth) and behaviour (testosterone-induced fighting in

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R. F. A. Weber
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M. P. Ooms
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J. T. M. Vreeburg
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ABSTRACT

The effects of hyperprolactinaemia on serum levels of LH were investigated in adult male rats of the R × U strain. Hyperprolactinaemia was induced by three pituitary grafts under the kidney capsule, transplanted on day 0 of each experiment. Special attention was paid to the contribution of prolactin-stimulated testes, adrenals and corticosterone.

In experiment 1, hyperprolactinaemia significantly reduced the serum concentrations of LH in intact rats. In spite of a significant increase in the serum levels of corticosterone, serum testosterone was not significantly affected by hyperprolactinaemia. The weights of both the adrenals and accessory sex glands were significantly increased at autopsy. In experiment 2, treatment with 10 mg corticosterone s.c. daily from day 14 to day 28 after pituitary grafting significantly reduced serum levels of both LH and testosterone. The suppression of testosterone in the hyperprolactinaemic corticosterone-treated animals was significantly less than in the corticosterone-treated control animals. The weights of the accessory sex glands were significantly increased in the hyperprolactinaemic animals. In experiment 3, rats were adrenalectomized and half of them were substituted with corticosterone. Serum testosterone levels significantly increased in both hyperprolactinaemic adrenalectomized rats and in adrenalectomized corticosterone-treated animals without any significant effect on serum LH. Again the weights of the accessory sex glands were significantly increased in the hyperprolactinaemic animals. In experiment 4, rats were adrenalectomized, gonadectomized and corticosterone treated on day 0 and then implanted with a 2, 1·5 or 1 cm silicone elastomer capsule containing testosterone. On day 28 after pituitary grafting, LH levels were significantly suppressed in animals with a 2 or 1·5 cm testosterone implant. The weights of the accessory sex glands were not increased in the hyperprolactinaemic animals.

These results show that in the male rat the inhibitory effects of hyperprolactinaemia on serum LH levels may be due to (1) increased sensitivity of the hypothalamic-pituitary axis to the negative feedback action of testosterone by prolactin and by the prolactin-stimulated corticosterone secretion and (2) stimulation of testicular testosterone secretion by prolactin, which can also explain the increased weights of the accessory sex glands. Even in the presence of high serum concentrations of corticosterone, stimulation of testicular testosterone secretion by prolactin was observed.

J. Endocr. (1987) 113,111–116

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R. F. A. Weber
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M. P. Ooms
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J. T. M. Vreeburg
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The effect of the transplantable prolactin- and ACTH-secreting tumour 7315a on male copulatory behaviour was investigated. Castrated tumour-bearing rats implanted with testosterone-filled capsules exhibited significantly longer latencies to first mount or intromission and to ejaculation than castrated control animals. In contrast to the number of intromissions, the number of mounts before ejaculation of the tumour-bearing rats was considerably increased. However, when castration was carried out in addition to adrenalectomy, the differences in copulatory behaviour between tumour-bearing rats and control rats were no longer present. During the last tests for copulatory behaviour the tumour-bearing rats had serum prolactin concentrations of more than 4000 ng/ml while control rats had less than 100 ng/ml. Plasma testosterone levels produced by silicone elastomer capsules were neither affected by the presence of the tumour nor by adrenalectomy. It was concluded that hyperprolactinaemia does not suppress the copulatory behaviour of adrenalectomized rats.

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A. Kooy
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R. F. A. Weber
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M. P. Ooms
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J. T. M. Vreeburg
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ABSTRACT

The effects of the transplantable purely prolactin-secreting tumour 7315b on serum gonadotrophins were studied in adult rats. Possible contributions of the adrenals to the tumour-induced inhibition of serum LH and FSH were evaluated. The suppressive actions of tumour 7315b on serum gonadotrophins in gonadectomized plus adrenalectomized male and female rats were compared.

Within 4 weeks after inoculation of tumour 7315b in intact male rats very high levels of prolactin and decreased serum levels of gonadotrophins and testosterone were recorded. At autopsy reduced weights of testes and accessory sex organs and slightly increased adrenal weights were found. In addition, in animals treated with a small testosterone-filled capsule after castration, tumour 7315b reduced serum concentrations of LH and FSH. Adrenalectomy did not prevent this suppressive action of the tumour on the post-castration rise of serum gonadotrophins. Suppression of serum gonadotrophins during hyperprolactinaemia was greater in gonadectomized plus adrenalectomized female rats than in male rats, indicating that the degree of the tumour-induced suppression of LH and FSH after castration is determined to a large extent by the sex of the animal.

The purely prolactin-secreting tumour 7315b has therefore been shown to be a suitable model for studying the effects of severe hyperprolactinaemia on the pituitary-gonadal axis in rats.

Journal of Endocrinology (1989) 120, 261–268

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R. F. A. Weber
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M. P. Ooms
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J. T. M. Vreeburg
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Pituitary glands were grafted under the capsule of the left testis of rats to induce high levels of prolactin in this organ. One hundred days after implantation, significantly increased levels of prolactin were found in the tissue and the venous plasma of the left testis. Although the levels of testosterone in testicular venous plasma were not raised, the testicular content of testosterone was increased when compared to the right testis. The ratio of testosterone and dihydrotestosterone was not affected in the pituitary-grafted testis.

Since the seminiferous tubules adjacent to the pituitary graft appeared to be completely normal, it is concluded that in the rat high levels of prolactin have no direct inhibitory effect on testicular functions.

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J. T. M. VREEBURG
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P. J. A. WOUTERSEN
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M. P. OOMS
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J. J. VAN DER WERFF TEN BOSCH
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Testosterone was measured in plasma pools from male and female fetal guinea-pigs between the ages of 30 and 55 days of pregnancy. Between days 33 and 36 the testosterone concentration in the plasma of males (1·4 ng/ml) was several times higher than that found at other ages or that measured in female fetuses. After infusion of tritiated testosterone for 2 h into pregnant guinea-pigs at day 36 of pregnancy, high levels of testosterone and androstenedione were found in maternal plasma. Nevertheless, tritiated testosterone and androstenedione could hardly be shown in the fetuses. Similar large differences in plasma progesterone levels appeared to exist between the maternal and the fetal circulation. Therefore, only a very small fraction of these steroids can penetrate from the maternal circulation into that of the fetus. This finding might be explained by the large difference in androgen-binding capacity between maternal and fetal plasma, as was shown by equilibrium dialysis.

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