EFFECTS OF DIHYDROTESTOSTERONE AND OESTRADIOL ON SEXUAL DIFFERENTIATION IN MALE RATS

1980 ◽  
Vol 84 (3) ◽  
pp. 397-407 ◽  
Author(s):  
P. VAN DER SCHOOT

Adult male rats which had been castrated at birth and treated with the non-aromatizable androgen dihydrotestosterone propionate (DHTP) showed incomplete copulatory behaviour. When tested with oestrous female rats during treatment with testosterone propionate (TP) they readily mounted these females and showed frequent penile intromissions but rarely ejaculated. In a long series of observations the proportion of ejaculating rats in tests of 30 min did not exceed 50%. Neonatally castrated rats treated with DHTP during infancy thus seemed to be capable of ejaculation in adulthood during treatment with TP, but the threshold for the occurrence of the ejaculatory reflex seemed to be higher than in normal male rats. By replacing treatment in adulthood with TP by a combined treatment with DHTP and oestradiol benzoate (OB), the frequency of ejaculation was not increased. It was concluded that the incomplete copulatory behaviour was not due to reduced efficiency of aromatization of androgen within the brain of these rats. The addition of OB to DHTP during the neonatal period of treatment enhanced the frequency of ejaculation in adulthood. The combined treatment of 0·1 mg DHTP on days 1, 3 and 5 with 0·01 mg OB on day 1 made adult copulatory behaviour during treatment with TP indistinguishable from that of rats castrated on day 10 or rats castrated at birth and treated with TP during infancy. It was concluded that the masculine organization of systems and structures involved in the display of male copulatory behaviour occurs under the influence of both non-aromatizable androgen and oestrogen, oestrogen being most likely the substance required to 'organize' the central nervous aspects of the regulation of this behaviour. The absence neonatally of nonaromatizable androgen and/or oestrogen results in specific deficiencies in adult copulatory behaviour as compared with the behaviour of normal male rats.

1977 ◽  
Vol 74 (3) ◽  
pp. 375-382 ◽  
Author(s):  
J. T. M. VREEBURG ◽  
PAULA D. M. VAN DER VAART ◽  
P. VAN DER SCHOOT

SUMMARY 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 0·25 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.


1974 ◽  
Vol 142 (2) ◽  
pp. 273-277 ◽  
Author(s):  
Jan-Åke Gustafsson ◽  
Åke Pousette

The regulatory mechanisms involved in the control of the nuclear NADPH-dependent 3-ketosteroid 5α-reductase (5α-reductase) activity were studied in liver, kidney and prostate. The substrate used was [1,2-3H]androst-4-ene-3,17-dione (androstenedione) (for liver and kidney) or [4-14C]androstenedione (for prostate). The hepatic nuclear 5α-reductase activity was greater in female than in male rats, was greater in adult than in prepubertal female rats, increased after castration of male rats, but was not affected by treatment with testosterone propionate or oestradiol benzoate. These regulatory characteristics are in part different from those previously described for the hepatic microsomal 5α-reductase. The renal nuclear metabolism of androstenedione, i.e. 5α reduction and 17β-hydroxy steroid reduction, was relatively unaffected by sex, age, castration and treatment with testosterone propionate. However, treatment of castrated male rats with oestradiol benzoate led to a significant increase in the 5α-reductase activity and a significant decrease in the 17β-hydroxy steroid reductase activity. Finally, the nuclear 5α-reductase activity in prostate was androgen-dependent, decreasing after castration and increasing after treatment with testosterone propionate. In conclusion, the nuclear 5α-reductase activities in liver, kidney and prostate seem to be under the control of distinctly different regulatory mechanisms. The hypothesis is presented that whereas the prostatic nuclear 5α-reductase participates in the formation of a physiologically active androgen, 5α-dihydrotestosterone, this may not be the true function of the nuclear 5α-reductase in liver and kidney. These enzymes might rather serve to protect the androgen target sites in the chromatin from active androgens (e.g. testosterone) by transforming them into less active androgens (e.g. 5α-androstane-3,17-dione and/or 5α-dihydrotestosterone).


1985 ◽  
Vol 5 (3) ◽  
pp. 393-400 ◽  
Author(s):  
Astrid Nehlig ◽  
Linda J. Porrino ◽  
Alison M. Crane ◽  
Louis Sokoloff

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the fluctuations of energy metabolism in discrete brain regions of female rats during the estrous cycle. A consistent though statistically nonsignificant cyclic variation in average glucose utilization of the brain as a whole was observed. Highest levels of glucose utilization occurred during proestrus and metestrus, whereas lower rates were found during estrus and diestrus. Statistically significant fluctuations were found specifically in the hypothalamus and in some limbic structures. Rates of glucose utilization in the female rat brain were compared with rates in normal male rats. Statistically significant differences between males and females at any stage of the estrous cycle were confined mainly to hypothalamic areas known to be involved in the control of sexual behavior. Glucose utilization in males and females was not significantly different in most other cerebral structures.


1987 ◽  
Vol 113 (3) ◽  
pp. 429-434 ◽  
Author(s):  
G. Forsberg ◽  
I. Bednar ◽  
P. Eneroth ◽  
P. Södersten

ABSTRACT Sexual receptivity was inhibited in ovariectomized rats treated with oestradiol benzoate (OB: two injections of 2 μg) and progesterone (0·5 mg) immediately after ejaculation by the male and restored after the end of the post-ejaculatory refractory period in the male. The post-ejaculatory inhibition of sexual receptivity was reversed by i.p. (5 mg), intracerebroventricular (50 μg) or intrathecal (50 μg) injection of the opioid peptide receptor antagonist naloxone. The concentration of serum β-endorphin-like immunoreactivity in ovariectomized rats treated with OB plus progesterone was unaltered by sexual interactions with males (18·3 ± 6·0 (s.e.m.), 26·4 ± 2·1 and 21·8 ± 6·1 pmol/l before sexual activity, after ejaculation and after the end of the post-ejaculatory interval) but reduced to non-detectable by hypophysectomy. Subcutaneous injection of 10 μg β-endorphin raised serum concentrations of β-endorphin-like immunoreactivity but did not affect the display of sexual behaviour. The behaviour was also unaffected by intracerebroventricular injection of 0·1, 0·2 or 1·0 μg β-endorphin or by injections of 0·25 μg β-endorphin in the periaqueductal central grey of the mesencephalon. The results show that ejaculation by male rats causes a transient inhibition of sexual receptivity in the female which may be dependent upon opioid peptide receptor mechanisms in the brain and spinal cord. It is unlikely that the peptide is β-endorphin. J. Endocr. (1987) 113, 429–434


1978 ◽  
Vol 78 (1) ◽  
pp. 31-38 ◽  
Author(s):  
G. VANDOREN ◽  
H. VAN BAELEN ◽  
G. VERHOEVEN ◽  
P. DE MOOR

Evidence is presented that the level of α2u-globulin in the serum of male rats depends, at least in part, on neonatal androgens. After castration of adult animals the concentration of this protein falls but remains measurable, whereas in intact or ovariectomized female rats α2u-globulin cannot be detected. Moreover, α2u-globulin is found in adult male and female rats gonadectomized at birth and treated with a single injection of testosterone propionate immediately thereafter. The mechanism by which neonatal androgens increase the concentration of α2u-globulin has been investigated. Transplantation of a supplementary pituitary gland under the renal capsule of male rats resulted in reduced levels of α2u-globulin and increased levels of transcortin. The changes discussed here were observed only in those animals in which the transplant was functional and they were amplified or reversed by modulators of prolactin secretion such as oestrogens or bromocriptine respectively. The hypothesis is advanced that neonatal androgens stimulate the production of a hypothalamic inhibitory factor that controls the secretion of prolactin, or another hypophysial hormone subjected to similar neuroendocrine control. Measurements in gonadectomized animals and in rats receiving both oestradiol benzoate and bromocriptine indicate that, besides these pituitary-mediated effects, both oestrogens and androgens exert direct effects on the level of α2u-globulin.


1973 ◽  
Vol 73 (1) ◽  
pp. 11-21 ◽  
Author(s):  
R. S. Swerdloff ◽  
P. C. Walsh

ABSTRACT The effects of androgens and oestrogens on serum LH and FSH in castrated rats were evaluated with regard to the modifying influences of duration of castration, duration of treatment and combined oestrogen-androgen effect. Serum LH was not greatly influenced by these variables. In contrast, serum FSH was shown to be more resistant to suppression by both steroids after at least five days of castration, requiring a longer duration of treatment to be suppressed to intact levels. Combined treatment of submaximally suppressive doses of testosterone propionate and oestradiol benzoate resulted in no additive effect on lowering serum FSH. Low doses of both androgens and oestrogens resulted in elevated levels of serum LH and FSH, suggesting that the adult male hypothalamic-pituitary axis may be responsive to positive feedback. In all studies, testosterone preferentially suppressed serum LH as compared to serum FSH. In contrast, oestradiol administration produced parallel inhibition of both LH and FSH. It is emphasized that neither oestrogen nor androgen alone, nor in combination, resulted in preferential inhibition of serum FSH over LH.


1974 ◽  
Vol 144 (2) ◽  
pp. 225-229 ◽  
Author(s):  
J-Å Gustafsson

The activities of the hepatic microsomal 2α-, 2β-, 7α- and 18-hydroxylase systems active on 5α-[4-14C]androstane-3α,17β-diol were studied in male and female rats which had been castrated at birth and at the age of 7, 13, 21, 27, 34, 43 and 55 days, treated for 5 days with 2mg of testosterone propionate/kg body weight and killed 6 days after castration. The 7α-hydroxylase system was affected very little by androgen treatment at all stages during development. On the other hand it was found that the rat liver passed through three phases during development with respect to androgen responsiveness as judged by changes in the activities of the 2α, 2β- and 18-hydroxylase systems: a first phase (from the neonatal period up to about 19 days of age) with a relative androgen unresponsiveness in both male and female rats, a second phase (from about 27 to about 33 days of age) when male and female rats responded equally well to androgens and a final phase (from about 40 days of age) with a successively decreasing androgen responsiveness in female rats but with a retained responsiveness in male rats. The hypothesis is presented that neonatal imprinting of the liver by testicular androgen(s) determines the development and degree of androgen responsiveness of liver tissue in the rat.


1976 ◽  
Vol 70 (3) ◽  
pp. 409-420 ◽  
Author(s):  
P. SÖDERSTEN

SUMMARY Sex differences in the lordosis response of adult rats to ovarian hormones were studied in a series of experiments. Male rats were less sensitive to oestradiol benzoate (OB, a single injection of 10, 100 or 1000 μg/kg or seven daily injections of 2, 10 or 50 μg/kg) than were female rats. Oestradiol benzoate-primed (10 μg/kg) female, but not male, rats showed dose-dependent responses to progesterone (0·4, 2·0 or 10·0 mg/kg). Male rats responded clearly to progesterone (2 mg/rat) only when primed with a high dose of OB (100 μg/rat). Display of the whole pattern of female sexual behaviour was induced in male rats by treatment with 100 μg OB and 2 mg progesterone. Female rats treated with 1 mg testosterone propionate (TP) on day 4 of life, ovariectomized as adults and tested under the same endocrine conditions as the rats described above, retained behavioural OB sensitivity but responded poorly to progesterone. Evidence is presented that ovarian secretions during development significantly modify the response of neonatally TP-treated and normal female rats to OB in adulthood.


1978 ◽  
Vol 76 (2) ◽  
pp. 233-240 ◽  
Author(s):  
P. SÖDERSTEN

Lordosis behaviour was induced in immature 20-day-old male rats by sequential treatment with oestradiol benzoate (OB) and progesterone, but prepubertal male rats were behaviourally less sensitive to the OB and progesterone treatment than were female rats. Thus, the sex difference in the lordosis response was present early during development. Castration at various times after birth showed that the capacity of immature rats to show lordosis is normally inhibited by an action of testicular secretions exerted during the first 10 days of life. Treatment of day 0 castrated rats with OB, either as a single injection given on the day of birth or as daily injections given on the first 10 days after birth, was much more effective in inhibiting the display of lordosis behaviour at 30 and 37 days of age than was treatment with testosterone benzoate (TB). Treatment with dihydrotestosterone benzoate neonatally had no inhibitory effect. Treatment of intact male rats or day 0 castrated OB-or TB-treated rats with the anti-oestrogen ethamoxytriphetol (MER-25) during the first 10 days of life antagonized the inhibitory effect of the testes and of the OB or TB treatment on the development of the lordosis response. It is suggested that during normal development oestradiol formed in the brain from testosterone in the circulation acts during the first 10 days of life to inhibit the capacity of male rats to show lordosis when adult.


1981 ◽  
Vol 91 (2) ◽  
pp. 325-334 ◽  
Author(s):  
MASAZUMI KAWAKAMI ◽  
JUN ARITA

Stimulation of the uterine cervix (CS) induced a nocturnal surge of prolactin at 04.00 h and a diurnal surge at 17.00 h in normal ovariectomized rats. However, the CS-induced prolactin surges did not occur in ovariectomized rats which had been treated with 250 μg testosterone propionate during the neonatal period. Chronic bilateral lesions of the suprachiasmatic nucleus (SCN) completely abolished the CS-induced nocturnal and diurnal surges of prolactin release which were observed in sham-lesioned, ovariectomized rats. Furthermore, bilateral lesions of the medial basal part of the suprachiasmatic area (MBSC), lying rostral to the SCN, were also effective in blocking the CS-induced nocturnal and diurnal surges. Lesions which destroyed mainly the optic chiasma and extended partially into the MBSC and SCN did not block the CS-induced prolactin surges. These results suggest that one reason for the failure of ovary-grafted male rats and neonatally androgenized female rats to maintain pseudopregnancy is the extinction of the circadian rhythm of the two daily prolactin surges, and that the MBSC, in addition to the SCN which is known to be a generator of other circadian rhythms, is involved in generation of the rhythm of prolactin surges.


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