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Search for other papers by I. J. DAVIES in
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SUMMARY
[7-3H]Pregnenolone was incubated with homogenates of adrenal glands from two 100-day-old sheep foetuses. Cortisol and corticosterone were isolated and identified by reverse isotope dilution and recrystallization to constant specific activity. Together these two compounds accounted for 12% and 17% of the substrate with the two tissue preparations. Other C21 and C19 metabolites which were sought were not present in appreciable quantities. Additional incubations were done with the adrenals of lamb foetuses ranging in age from 110 days of gestation to the immediate newborn period. Glucocorticoidogenic capacity similar to that of the 100-day-old foetuses was demonstrated throughout this period and no age-related change was evident. These results demonstrate that the lamb foetal adrenal has a substantial enzymic capacity for glucocorticoid synthesis throughout at least the last third of gestation. In conjunction with the observations of others, these experiments support the hypothesis that during this period of gestation the lamb foetal adrenal is actively synthesizing glucocorticoids in a manner which is similar to the lamb at term and the adult sheep.
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Limbic structures have been implicated in the control of gonadotrophin secretion and sexual behaviour in immature and mature animals and human beings (Schreiner & Kling, 1956; Critchlow & Elwers Bar-Sela, 1967; Velasco & Taleisnik, 1969; Harris & Naftolin, 1970). Although little is known of their cellular metabolism, these areas have been shown to bind radioactivity after the injection of androgens or oestrogens in the intact animal (Pfaff, 1968; Stumpf, Baerwaldt & Sar, 1970). The finding of aromatization of androgens by human foetal hypothalamus (Naftolin, Ryan & Petro, 1971) prompted us to look for the existence of similar enzyme systems in limbic tissues.
Central nervous system tissue was dissected from two 17-week-old (11·5 and 10·5 cm crown-rump length) male foetuses within 30 min of hysterotomy at therapeutic abortions done for psychiatric indications. The pregnancies had been unremarkable and no abnormalities were found in the foetuses. Limbic tissue was sharply dissected utilizing
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SUMMARY
Pregnant rabbits were treated with indomethacin (8–10 mg/kg/day) or dexamethasone (1·2–1·8 mg/kg/day) during late gestation. The effects of these treatments on the concentrations of progesterone and prostaglandin F (PGF) in the peripheral plasma, and the outcome of gestation were studied. Treatment with indomethacin significantly prolonged the length of gestation (P < 0·01) compared with control, untreated animals. In these treated animals, the plasma progesterone levels declined at a similar time to that in control rabbits but the increase in systemic PGF normally seen during late pregnancy was reduced. Dexamethasone treatment reliably induced premature delivery within 3–6 days. The plasma progesterone concentration fell rapidly during the first 24 h of dexamethasone administration, but in no animal was this associated with a significant increase in the plasma levels of PGF.
These results are consistent with the suggestion that prostaglandins are involved in the normal initiation of parturition in the rabbit. They do not support the hypothesis that the effect of dexamethasone on the length of gestation is mediated through an increase in the production of prostaglandin F.
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Recent in-vivo and in-vitro experiments have revealed a discordance in the ability of the brain and adenohypophysis from man, monkeys, rats and rabbits to form oestrone from testosterone, and oestradiol-17β from androstenedione (Naftolin, Ryan & Petro, 1971a, b; Flores, Naftolin & Ryan, 1973; Flores, Naftolin, Ryan & White, 1973; Reddy, Naftolin & Ryan, 1973). To examine this question further, central tissues from untreated adult virgin female and male New Zealand White rabbits were incubated in vitro with [3H]oestrone, [14C]androstenedione or [14C]testosterone under conditions identical to those described in the above reports. After dissection, the tissues were homogenized and incubated with approximately 2 μCi of one of the above steroids (all obtained from New England Nuclear Corp.) in the presence of an NADPH-generating system, except for the omission of glucose 6-phosphate and glucose 6-phosphate dehydrogenase during the testosterone incubations. After incubation of oestrone, oestradiol-17β was
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ABSTRACT
It has been proposed that a seasonal increase in oestradiol negative feedback elicits anoestrus by preventing a key step in the preovulatory sequence of endocrine events, namely a sustained increase in tonic LH secretion. In the present study we compared the patterns of serum LH, FSH, oestradiol and progesterone after regression of the last corpus luteum of the breeding season, with their respective patterns during an ovulatory cycle in the late breeding season (samples obtained every 4 h from eight ewes). After regression of the last corpus luteum of the breeding season, serum LH and oestradiol showed distinct deviations from their respective late breeding season patterns. The rise in tonic LH secretion was curtailed. Further, there were no marked increases in oestradiol, despite a distinct, although brief, tonic LH rise; thus there were no gonadotrophin surges. If the hypothesis that the transition into anoestrus is caused solely by insufficient tonic LH secretion were correct, the brief increase in LH should have induced a transient rise in oestradiol. Since this was not the case, these results suggest that a decreased ovarian response to LH may also contribute to the termination of oestrous cyclicity at the transition to anoestrus.
J. Endocr. (1985) 106, 55–60
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Seasonal variations in the behavioural and feedback actions of oestradiol in the ewe were examined by determining the ability of various physiological oestradiol concentrations to elicit oestrous behaviour, induce an LH surge, and suppress tonic LH secretion at four times of the year. These tests were performed in acutely ovariectomized animals pretreated with oestradiol and progesterone to minimize seasonal differences in their endocrine status. Although smaller amplitude LH surges were observed in anoestrus, the dose–response curves for the induction of LH surges were virtually identical at all times of the year. Oestradiol was slightly less effective in eliciting oestrous behaviour in anoestrus and during the transition to the breeding season than at other times. This seasonal variation was, however, observed only with relatively low oestradiol concentrations; serum oestradiol levels of 3 pg/ml or greater induced oestrus in almost all ewes regardless of season. In contrast, there was a marked seasonal change in the negative feedback action of oestradiol. In anoestrus, basal oestradiol levels of 1–3 pg/ml suppressed LH to low levels (0·3 ng/ml), whereas in the breeding season, even peak oestradiol concentrations of 10 pg/ml were not able to produce this degree of inhibition. These results thus support the hypothesis that the annual breeding cycle of the ewe is governed primarily by shifts in the extent to which oestradiol can suppress tonic LH secretion.
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Department of Obstetrics and Gynecology, and Laboratory of Human Reproduction and Reproductive Biology, Harvard Medical School, Boston, Massachusetts 02115, U.S.A.
(Received 19 May 1975)
Testosterone and its ring A reduced metabolite, dihydrotestosterone (DHT), lower gonadotrophin concentrations in weaned rats (Swerdloff, Walsh & Odell, 1972; Naftolin & Feder, 1973). While neonatally administered testosterone causes anovulatory sterility in adult female rats, similar treatment with DHT has no apparent effect upon central neuroendocrine programming (Brown-Grant, Munck, Naftolin & Sherwood, 1971; Whalen & Luttge, 1971), which raises the question of whether DHT can suppress gonadotrophins in the neonatal rat.
In the first experiment, 5-day-old Sprague–Dawley-derived rats (Charles River Farms) were injected s.c. with 100 μg DHT propionate (DHTP), 100 μg testosterone propionate (TP, Eli Lilly & Co.) or the sesame oil diluent, and allowed to develop without further treatment. The injection volume was 25 μl. All animals were weaned on day 20. Daily vaginal
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AgResearch Ltd, Hamilton, New Zealand
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Insulin-like growth factor-1 (IGF1) is crucial for regulating post-natal growth and, along with myostatin (MSTN), regulates muscle size. Here, we sought to clarify the roles of these two genes in regulating sexually dimorphic growth of body and muscle mass. In the first study, we established that Igf1 mRNA was increased to a greater extent and Igf1 receptor mRNA increased earlier in male, than in female, gastrocnemius muscles during the rapid phase of growth (from 2 to 6 weeks) were unchanged, thereafter, to 32 weeks of age in WT mice (P < 0.001). In the second study, we sought to determine if supplemental IGF1 could overcome the sexual dimorphism of muscle and body mass, when myostatin is absent. We crossed myostatin null (Mstn –/– ) mice with mice over-expressing Igf1 in skeletal muscle (Igf1 +) to generate six genotypes; control (Mstn+/+ ), Mstn +/– , Mstn –/– , Mstn+/+ :Igf1 +, Mstn +/– :Igf1 + and Mstn –/– :Igf1 + (n = 8 per genotype and sex). In both sexes, body mass at 12 weeks was increased by at least 1.6-fold and muscle mass by at least 3-fold in Mstn –/– :Igf1 + compared with Mstn+/+ mice (P < 0.001). The abundance of AKT was increased in muscles of mice transgenic for Mstn, while phosphorylation of AKTS473 was increased in both male and female mice transgenic for Igf1+ . The ratio of phosphorylated to total AKT was 1.9-fold greater in male mice (P < 0.001). Thus, despite increased growth of skeletal muscle and body size when myostatin was absent and IGF1 was in excess, sexual dimorphism persisted, an effect consistent with greater IGF1-induced activation of AKT in skeletal muscles of males.
