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ABSTRACT
Maximal incremental changes in plasma LH were compared in adult hens and cockerels after i.v. injection of chicken (c) LHRH-I (pGlu1-His2-Trp3-Ser4-Tyr5-Gly6-Leu7-Gln8-Pro9-Gly10-NH2) or cLHRH-II (pGlu1-His2-Trp3-Ser4-His5-Gly6-Trp7-Tyr8-Pro9-Gly10-NH2). The LH response to cLHRH-I and -II was more rapid and greater in cockerels than in hens. The potencies of the two decapeptides were the same in cockerels but different in hens. Relative to cLHRH-I, the potency of cLHRH-II was 0·91 (0·6– 1·2; 95% confidence limits) in cockerels and 36·5 (16·8–128·6) in hens.
The greater potency of cLHRH-II relative to cLHRH-I in the hen than in the cockerel could not be accounted for by sex differences in the half-lives of the decapeptides in the peripheral circulation. The half-lives of both decapeptides in hens and cockerels ranged between 2·42 and 3·77 min.
It is concluded that the interaction between LHRH-I and -II and the gonadotrophs is sexually differentiated in the domestic fowl.
A new homologous radioimmunoassay was established for cLH. As in other chicken LH radioimmunoassays, there was evidence of cross-reactivity with TSH.
J. Endocr. (1987) 115, 323–331
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ABSTRACT
The macromolecular content (DNA, soluble proteins and ovalbumin) of the magnum and the plasma concentrations of oestradiol and progesterone were studied during sexual development of the Japanese quail. Rapid growth and differentiation of the magnum began between 21 and 28 days of age and rapidly reached the laying stage in about 20 days. This rapid change in magnum size occurred in a stepwise manner: cellular proliferation was observed first, followed by the synthesis and accumulation of specific proteins. Just before and during magnum growth, plasma oestradiol and progesterone concentrations followed different patterns: the initiation of epithelial cell proliferation was preceded by a sharp decrease in plasma progesterone. Maximum cell division occurred while plasma progesterone levels continued to decrease slightly; at the same time, oestradiol increased from 0·098 to 0·453 nmol/l. The decrease and finally the cessation of cell proliferation and the concomitant increase in ovalbumin concentration were related to almost constant levels of plasma oestradiol and increasing levels of plasma progesterone. Further development of the magnum (above 2·3 g weight) involving only the accumulation of secretory products was associated with an increased value of plasma progesterone. These data are consistent with the hypothesis that there are multiple hormonal signals controlling cell proliferation and synthesis of egg-white proteins in the oviduct. Progesterone may be one of the key signals that regulates the initiation of oviduct growth in the quail.
J. Endocr. (1984) 100, 167–173
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Geoffrey Harris, while still a medical student at Cambridge, was the first researcher (1937) to provide experimental proof for the then tentative view that the anterior pituitary gland was controlled by the CNS. The elegant studies carried out by Harris in the 1940s and early 1950s, alone and in collaboration with John Green and Dora Jacobsohn, established that this control was mediated by a neurohumoral mechanism that involved the transport by hypophysial portal vessel blood of chemical substances from the hypothalamus to the anterior pituitary gland. The neurohumoral control of anterior pituitary secretion was proved by the isolation and characterisation of the ‘chemical substances’ (mainly neuropeptides) and the finding that these substances were released into hypophysial portal blood in a manner consistent with their physiological functions. The new discipline of neuroendocrinology – the way that the brain controls endocrine glands and vice versa – revolutionised the treatment of endocrine disorders such as growth and pubertal abnormalities, infertility and hormone-dependent tumours, and it underpins our understanding of the sexual differentiation of the brain and key aspects of behaviour and mental disorder. Neuroendocrine principles are illustrated in this Thematic Review by way of Harris' major interest: hypothalamic–pituitary–gonadal control. Attention is focussed on the measurement of GnRH in hypophysial portal blood and the role played by the self-priming effect of GnRH in promoting the onset of puberty and enabling the oestrogen-induced surge or pulses of GnRH to trigger the ovulatory gonadotrophin surge in humans and other spontaneously ovulating mammals.
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SUMMARY
Spontaneous gonadotrophin release and the gonadotrophin response to LH releasing factor (RF) were studied in pro-oestrous, androgenized female and male rats. The animals were either intact or gonadectomized (about 32 h previously) and treated with various steroids. The gonadotrophin response (especially LH) was much lower in intact males and androgenized females than in pro-oestrous females. Oestrogen plus progesterone increased plasma gonadotrophin concentrations and responses in ovariectomized rats, but inhibited the increase in the plasma gonadotrophin concentration and the LH response which followed castration in males. As in the normal female, ovariectomy decreased the LH response but increased the plasma FSH concentration and response in the androgenized female; oestrogen and progesterone had relatively little effect. Apart from reducing the postcastration rise in plasma FSH, testosterone had no significant effect in gonadectomized male or female animals. These results show that the effect of steroids on the gonadotrophin response to LH-RF as well as the spontaneous secretion of gonadotrophin depends upon sexual differentiation of the hypothalamo-hypophysial system. Studies with various metabolites of progesterone indicated that the facilitatory action of this steroid could be due, in part, to a 5α-reduced derivative.
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ABSTRACT
Hepatic microsomal testosterone 5-reductase activity was approximately fourfold higher in adult female rats than in males. This discrepancy was only partly androgen-dependent since gonadectomy of male rats at 68 days of age resulted in only a partial increase of the enzyme activity. This increase was reversible by the administration of testosterone. Similar treatment, however, produced no effect in the female rat, indicating that there is a sex difference in testosterone responsivity. Castration of newborn male rats resulted in a marked increase in the basal enzyme activity. This increase was not affected by treating the adults with testosterone. Giving testosterone to male rats immediately after neonatal gonadectomy, or to newborn female rats, did not produce the male pattern of both the basal enzyme activity and the testosterone responsivity in adulthood. These results suggest that a brief exposure to neonatal androgen is not critical for the expression of the male type of enzyme activity, but that the continuous presence of the male gonads up to and including the pubertal period is essential. Exposure of pubescent female rats to testosterone during the period from 35 to 50 days of age resulted in a significant increase in testosterone sensitivity when tested at 90 days of age, suggesting that pubertal exposure to androgen is important for the expression of testosterone responsivity in adulthood. The sensitivity was potentiated when the animals were ovariectomized before puberty. Furthermore, the enzyme activity in prepubertally ovariectomized female rats was significantly lower than that in adult gonadectomized animals. The decreased level of activity returned to the control value when oestrogen was replaced during puberty, indicating that peripubertal oestrogen exposure is required for maintaining the high level of activity found in adult female rats. The present findings suggest that the pubertal period represents a sensitive phase during which sex hormones act to regulate the sexual differentiation of testosterone 5-reductase activity in the rat.
J. Endocr. (1985) 106, 71–79
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The effect of increasing gestational age and maternal exposure to cannabinoids on body weight, ano-genital distance and androgen concentration in fetal mice was examined. Body weight increased in both male and female fetuses from days 16 to 18 (the presence of a vaginal plug was considered to indicate day 1 of pregnancy), while ano-genital distances tended to increase faster in male than in female fetuses. The concentration of testosterone increased with age in fetuses of either sex. However, at day 16, there was a significant influence of fetal sex on testosterone concentration with two non-overlapping distributions, one above and one below 300 pg/g fetal tissue, correlating with male and female gender respectively. After day 16, male fetuses tended to have higher testosterone concentrations, but some values obtained in females did overlap.
Treatment of female mice with Δ9-tetrahydrocannabinol, the main psychoactive ingredient of marihuana, from days 12 to 16 of pregnancy caused a significant (P < 0·01) increase in fetal deaths in utero. Cannabinol treatment had no effect on this parameter, but reduced body weight (P < 0·02) in female fetuses, and increased ano-genital distance (P < 0·05) in male fetal mice. The concentrations of testosterone and dihydrotestosterone were reduced in male but not in female fetuses.
The results indicate that exposure to psychoactive or non-psychoactive constituents of marihuana suppresses testosterone levels in fetal as well as in immature and adult mice, as we have previously reported. Thus, maternal exposure to cannabinoids may interfere with the process of sexual differentiation in their male offspring as a result of decreased fetal androgen production.
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– 298 . ( doi:10.1016/j.cytogfr.2010.06.001 ) MacLaughlin DT Donahoe PK 2004 Sex determination and differentiation . New England Journal of Medicine 350 367 – 378 . ( doi:10.1056/NEJMra022784 ) Morgan K Dennis NA Ruffman T Bilkey DK
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The major purpose of this study was to characterize the open-loop frequency of pulsatile GnRH release in the female rhesus monkey at an age (15-20 months) when the prepubertal restraint on the hypothalamic-pituitary axis is maximally imposed. Additionally, evidence for pulsatile GnRH release in agonadal males of comparable age was also sought. Episodic LH secretion from the pituitary was used as an indirect index of GnRH discharges. In order to maximize the sensitivity of this in situ bioassay, the responsiveness of the pituitary gonadotrophs was usually first heightened by an i.v. intermittent infusion of the synthetic peptide. Monkeys (five females, three males) were castrated between 9 and 14 months of age, implanted with indwelling venous catheters, fitted with nylon jackets and housed in specialized cages that permitted remote access to the venous circulation with minimal restraint and without interruption of the light-darkness cycle. In females, LH secretion was generally assessed at 20-day intervals during alternate nighttime (1900-0200 h) and daytime (0700-1400 h) windows. In males, LH was assessed less frequently and only at night. The mean frequency of pulsatile LH release in agonadal prepubertal females was 4 pulses/7 h during the night and 2 pulses/7 h during the day. These findings indicate that, prior to puberty in the female monkey, the GnRH pulse generator operates at a relatively slow frequency and is subjected to diurnal modulation. In males, evidence for robust pulsatile GnRH release was not observed. The striking difference in activity of the GnRH pulse generator in agonadal prepubertal male and female monkeys reinforces the view that the ontogeny of the hypothalamic drive to the pituitary-gonadal axis in higher primates, including man, is sexually differentiated.
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in male sexual development Whereas the importance of testosterone in sexual differentiation, both in early development and around puberty, is beyond dispute, the impact of testosterone on the emergence of sexual arousability is less
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SUMMARY
The metabolism of [4-14C]4-androstene-3,17-dione was studied in the 105000 g microsomal and supernatant fractions of liver from developing rats of both sexes. The following enzyme activities were measured: 5β-reductase (supernatant fraction) and 5α-reductase, 17α- and 17β-hydroxysteroid reductases, 6β-, 7α- and 16α-hydroxylases (microsomal fraction). The activities of the 3α- and 3β-hydroxysteroid reductases were estimated by calculating the ratios of 3α-:5α- and 3β-: 5α-reduced metabolites formed, respectively.
Most enzyme activities present at birth (i.e. 5β-reductase, 5α-reductase, 17β-hydroxysteroid reductase, 6β- and 7α-hydroxylase) increased until 20 days of age in both male and female rats. Between 20 and 30 days of age a number of masculine metabolic characteristics appeared in both sexes, i.e. the 16α-hydroxylase and the 17α-hydroxysteroid reductase were induced, the 5β-reductase activity rapidly increased and the 5α-reductase activity slightly decreased. During a third period beginning 30 days after birth the adult male enzyme activity pattern was completed by the induction of 3β-hydroxysteroid reductase and a further increase in the activity of 16α-hydroxylase. After 30 days of age a feminine type of liver metabolism also rapidly developed in female rats; the 16α-hydroxylase and the 17α-hydroxysteroid reductase activities disappeared, the 6β-hydroxylase and the 5β-reductase activities decreased and the 5α-reductase activity increased six times.
The developmental patterns of enzyme activities in the rat liver are consistent with a first developmental phase (0–30 days of age) independent of hypophysial control and probably determined primarily by the genome of the liver cell and a second phase (from 30 days onwards) with increasing sexual differentiation under hypophysial control. This control is mediated by some kind of feminizing factor in female rats and possibly by some kind of androgen-elicited secretion of masculinizing factor(s) in male rats.
The metabolism of [4-14C]4-androstene-3,17-dione was also studied during different times of the day and during different phases of the oestrous cycle. The 16α-hydroxylase activity showed a diurnal variation with higher values at noon than at midnight. The 5β-reductase activity reached a maximal activity during metoestrus.
