A receptor mediating sexual differentiation?

Barley, Jackie; Ginsburg, M.; Greenstein, Ben; MacLusky, Neil J.; Thomas, Patrick J.

doi:10.1038/252259a0

Cited by 94 publications

(15 citation statements)

References 16 publications

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“…The observation that only aromatizable androgens and oestrogens themselves (Gorski, 1963;Whalen & Nadler, 1963) are active, and the finding of oestradiol receptors in the neonatal rat brain (Barley, Ginsburg, Greenstein, McLusky & Thomas, 1974) have led to the concept that in the male rat, masculinization of the brain occurs after the local conversion of androgens to oestrogens. This concept is further supported by the observation that in neonatal female rats, the action of exogenous testosterone can be inhibited by the anti-oestrogen MER-25 (McDonald & Doughty, 19726).…”

Section: Introductionmentioning

confidence: 98%

Prevention of Central Defeminization but Not Masculinization in Male Rats by Inhibition Neonatally of Oestrogen Biosynthesis

Vreeburg¹,

Vaart²,

Schoot³

1977

Journal of Endocrinology

146

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An inhibitor of aromatization, androsta-1,4,6-triene-3,17-dione (ATD), was administered to newborn male and female rats and various parameters of gonadal and sexual function were examined in adulthood. Males injected with 1 mg ATD on the day of birth (day 1) and on days 3, 5, 10 and 15 postnatally, subsequently (day 55) showed normal male and female copulatory behaviour, but were not able to maintain cyclicity in ovarian transplants. When the ATD was administered by Silastic implants, however, cyclicity in ovarian transplants did occur. Neither form of treatment brought about significant changes in neonatal plasma or testicular testosterone concentrations.Female rats implanted on day 3 of life with Silastic capsules containing ATD and then given an injection of 0\m=.\25 mg testosterone propionate on day 5 subsequently showed normal ovarian function, whereas the controls receiving only testosterone propionate showed persistent vaginal cornification, anovulation and polyfollicular ovaries.The results support the view that the central conversion of testicular androgens to oestrogens during the neonatal period is necessary to abolish cyclic gonadotrophin release and to suppress female copulatory behaviour.

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Section: Introductionmentioning

confidence: 98%

Prevention of Central Defeminization but Not Masculinization in Male Rats by Inhibition Neonatally of Oestrogen Biosynthesis

Vreeburg¹,

Vaart²,

Schoot³

1977

Journal of Endocrinology

146

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“…Non-aromatizable androgens lack these effects (Booth, 1977a). Aromatizing enzymes and a specific oestradiol receptor are present in the cytosol fraction of the brains of newborn rats of both sexes (Barley, Ginsburg, Greenstein, MacLusky & Thomas, 1974;Reddy, Naftolin & Ryan, 1974) and a nuclear oestradiol receptor binds oestrogen in the hypothalamus of the newborn male rat, where oestrogen is presumed to act (Westley & Salaman, 1976). Injections of the anti-oestrogen MER-25 can prevent the normal suppression of female sexual behaviour and organization of male sexual behaviour in intact newborn rats (Booth, 19776;Södersten, 1978).…”

Section: Introductionmentioning

confidence: 99%

Effects of the Aromatization Inhibitor Androst-4-Ene-3,6,17-Trione on Sexual Differentiation Induced by Testosterone in the Neonatally Castrated Rat

Booth¹

1978

Journal of Endocrinology

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Groups of rats were castrated on the day of birth (day 1) and injected with testosterone, androst-4-ene-3,6,17-trione (ADT, an inhibitor of aromatization), testosterone + ADT or oil daily from day 1 to day 5. The aromatizable androgen testosterone suppressed both cyclic gonadotrophin secretion, as judged from the absence of corpora lutea in grafted ovaries, and the behavioural response to injections of oestradiol benzoate and progesterone in adulthood. It also stimulated normal development of the penis and ejaculation in behaviour tests carried out after injections of testosterone propionate. The aromatization inhibitor ADT, like oil, did not affect either cyclic gonadotrophin secretion or receptive behaviour, but injections of ADT given at the same time as testosterone significantly reduced the effects of the androgen on both cyclic gonadotrophin secretion and receptive behaviour. Although neonatal administration of ADT did not affect the testosterone-stimulated development of the penis or the ability of the rats to achieve penile intromissions, it did interfere with ejaculation. None of the rats which had been injected with testosterone+ADT ejaculated. These results support the concept that during infancy neural conversion of androgens to oestrogens is important both for the suppression of the female patterns of gonadotrophin secretion and sexual behaviour and for the central organization of normal patterns of male sexual behaviour. Normal completion of the differentiation of the male genital tract appears to be independent of the central organization of masculine patterns of sexual behaviour.

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“…However, recent evidence has suggested that neonatal exposure to testosterone, which may be converted into oestrogen in the hypothalamus, is actually required for normal development of female sexual behaviour (Christensen & Gorski, 1978). The occurrence ofcytosol oestrogen receptors in the hypothalamus of the female neonatal rat has been reported Barley et al, 1974;Westley et al, 1976). However, their role remains ill-defined.…”

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confidence: 96%

Developmental changes in the content of oestrogen receptors in the hypothalamus of the female rat

White¹,

Hall²,

Lim³

1979

Biochemical Journal

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Hypothalamic cytosol and nuclear oestrogen receptors are present at birth. A 2-fold increase in cytoplasmic receptor content occurs by the second week, whereas the first significant and equivalent increase in nuclear receptor occurs in the fourth week. The latter reflects reported increases in oestradiol availability thought to lead to complete feminine sexual differentiation. The presence of nuclear receptors in the newborn suggests a requirement for oestrogenic stimulation in early development.Sexual differentiation of the rat hypothalamus occurs post-natally. During the first 10 days after birth the administration of androgens or oestrogens to the female results in 'masculinization' of the hypothalamus, with attendant abnormalities in the pattern of gonadotropin release and sexual behaviour as adults (Gorski, 1971). Because of this effect, sexual differentiation of the hypothalamus of the female has been considered to be independent of oestrogen, which is prevented from interacting with the hypothalamus by the oestrogen-binding a-foetoprotein present in plasma (McEwen et al., 1975). However, recent evidence has suggested that neonatal exposure to testosterone, which may be converted into oestrogen in the hypothalamus, is actually required for normal development of female sexual behaviour (Christensen & Gorski, 1978). The occurrence ofcytosol oestrogen receptors in the hypothalamus of the female neonatal rat has been reported Barley et al., 1974;Westley et al., 1976). However, their role remains ill-defined. In this paper we report on the nucleocytoplasmic relationships of the oestrogen receptor in the first 4 weeks post partum and on the presence of nuclear receptors in the hypothalamus of the neonatal female rat. The latter finding suggests the occurrence of oestrogen-stimulated translocation of receptor in the newborn. In addition, we have observed binding of the cytosol receptor to oligo(dT)-cellulose, which in the adult has been proposed to serve as an index for nuclear binding of receptor in vivo (Thrower et al., 1976; White et al., 1978). This binding demonstrates that the potential for nuclear binding of receptor exists in these neonatal animals. ExperimentalFemale Wistar rats from our animal colony were used. In experiments to study the effect of oestradiol * To whom reprint requests should be addressed. Vol. 184 on nuclear receptor content, 2.5pg of oestradiol-1716 was administered intraperitoneally in 0.1 ml of 25% (v/v) ethanol in saline (0.9 % NaCI) and animals were killed 6h later.Oestradiol-receptor content was measured in nuclear and cytosol preparations obtained from hypothalamic tissue as previously described (White, 1978; White et al., 1978). Briefly, nuclear receptor measurements involved incubation of nuclear fractions at 37°C for 1 h with saturating concentrations of [3H]oestradiol (Anderson et al., 1973).The nuclear content of receptor per hypothalamic block was independent of the weight of the block (r = 0.35; n = 22) over the weight range 0.1-0.24g (White, 1978). Expression of nuclear...

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A receptor mediating sexual differentiation?

Cited by 94 publications

References 16 publications

Prevention of Central Defeminization but Not Masculinization in Male Rats by Inhibition Neonatally of Oestrogen Biosynthesis

Prevention of Central Defeminization but Not Masculinization in Male Rats by Inhibition Neonatally of Oestrogen Biosynthesis

Effects of the Aromatization Inhibitor Androst-4-Ene-3,6,17-Trione on Sexual Differentiation Induced by Testosterone in the Neonatally Castrated Rat

Developmental changes in the content of oestrogen receptors in the hypothalamus of the female rat

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