The effect of testosterone during the neonatal period on the thyroid gland of male and female rats

Abstract

The essential features of the syndrome produced by androgenic hormone administration during the neonatal period in female rats-precocious vaginal opening, persistent vaginal cornification and failure of spontaneous ovulation which can, however, be produced by the administration of exogenous luteinizing hormone, were all described by Pfeiffer (1936).In his work, male hormone was received as a consequence of the grafting of testicular tissue. Later workers (see Takewaki, 1962 for references) have generally employed a single injection of an androgen, usually testosterone (17fl-hydroxyandrost-4-en-3-one) to produce this syndrome experimentally at will. The normal adult female rat that is undergoing regular oestrus cycles shows a cyclic variation in the level of thyroid-gland activity in phase with the ovarian cycle, activity being greatest during the oestrus stage (Brown-Grant, 1962). The changes in the thyroid may be related to events in the hypothalamus and pituitary leading to a discharge of luteinizing hormone and hence ovulation (Brown-Grant, 1963a). The absence of ovulation in the androgen-treated female rat may be due to a failure of the hypothalamic mechanism involved in the cyclic release of LH (Barraclough, 1963) and a study of possible alterations in the level of the thyroid-gland activity in such animals is reported here. Some of the preliminary findings have been referred to in a short note published previously (Brown-Grant, 1963a).Animals exhibiting the syndrome have been referred to by different workers as constant-oestrus rats, androgen-sterilized rats or 'anovulatorypersistent-oestrus' rats, but as these animals do not show normal female mating behaviour and the cornification of the vaginal smear is not constant, and ovulation can be produced by electrical stimulation of the brain, none of these names are satisfactory. The term testosterone propionate treated rats (TP rats) will be used here.

Facilitation of Luteinizing Hormone Secretion in the Female Rat by Progesterone

“…Oestrus' was 96 or 120 h after injection. In agreement with earlier studies, such as those of Gorski & Barra¬ clough (1962) and of Brown-Grant (1965), this treatment did not induce ovulation.…”

The 'Early Androgen Syndrome' in the Guinea-Pig

“…Ovarian weight is increased rather than decreased and an increase in adrenal weight even above the levels seen in control animals at about the time of behavioural oestrus was a constant feature of the syndrome (Table 5). In the rat, ovarian weight is reduced and though adrenal hypertrophy has been reported (Barraclough, 1961) this is by no means a consistent finding (Barraclough & Gorski, 1961 ;Brown-Grant, 1965;Harris & Levine, 1965;Matsuyama, Weisz &Lloyd, 1966). Similarly, an increase in pituitary weight is not a consistent finding in the rat (Matsuyama et al 1966) as it is in the guinea-pig nor have marked histological changes been reported although Self (1966) indicated that the proportion of basophils was somewhat reduced and that the number of eosinophils, identified histologically as luteotrophin-containing cells, was increased.…”

“…Finally, the changes observed in the uterus appear to have no parallel in the rat. In the rat, uterine weights are generally inter¬ mediate between the high values observed at pro-oestrus and the low values charac¬ teristic of dioestrus in normal animals (Brown-Grant, 1965). Indeed there is evidence that, at least after high doses of androgen, the capacity to respond to exogenous oestrogen may be impaired (Harris & Levine, 1965) possibly because of a reduction in the number of 'oestrogen receptors' (Flerkó, Mess & Illei-Donhoffer, 1969).…”

The relationship between ovulation and the changes in thyroid gland activity that occur during the oestrous cycle in rats, mice and hamsters

“…OVULATION AND THE THYROID 403 of testosterone during the neonatal period (Brown-Grant, 1963, 1965b, and from studies of pregnant and pseudopregnant rats (Brown-Grant, 1965a). It was not clear, however, whether the postulated discharge of TSH was directly associated with the neuroendocrine changes leading to the ovulatory discharge of LH or whether the sequence of events was hypothalamic stimulation of LH release leading to a change in ovarian steroid secretion, the steroids acting on the pituitary or hypothalamus to induce TSH discharge.…”