Reversal by progesterone of phenobarbitone blockade of ovulation in the prepubertal rat primed with pregnant mare serum gonadotrophin.

In immature female rats injected with PMSG at 30 days of age (day 30), ovulation occurs between the hours of 02.00 and 03.00 on day 33. If progesterone is injected at 10.00 h on day 32, the onset of ovulation is advanced by 1-2 h. In rats that were not given progesterone, ovulation was blocked by phenobarbitone sodium administered on day 32 before 13.50 h. However, pretreatment with progesterone at 10.00 h caused ovulation to occur in spite of phenobarbitone treatment at 13.50 h. An early release of ovulatory gonadotrophin from the anterior pituitary gland cannot completely account for progesterone's capacity to reverse the blockade of ovulation by phenobarbitone, because when phenobarbitone treatment was advanced by 2-4 h, ovulation still occurred in most progesterone-treated rats.     

Temporal relationship between the onset of daily gonadotrophin surges and of puberty in female golden hamsters

Daily rhythms of LH and FSH release commence on day 16 or 17 of age in the prepubertal female golden hamster, 2-3 weeks before regular 4-day oestrous cycles begin. We tested the hypothesis that the daily surges of gonadotrophin regulate, at least in part, rate of sexual maturation and, hence, age at puberty. We predict that an advance or a delay in the initiation of the daily rhythm should result in a corresponding advance or delay in the day of puberty. In the first test, the onset of daily gonadotrophin surges was advanced by gonadotrophin-releasing hormone (GnRH) injections; in the second test, the onset was delayed by daily injection of phenobarbital sodium (PB). The day of the first of at least three consecutive post-ovulatory vaginal discharges was used as an index of the age at puberty. Gonadotrophin-releasing hormone (50 ng/0.1 ml saline per animal) was injected at 16.30 h on days 8-17 of age. These injections initiated a daily mid-afternoon surge of LH about 8 days before the onset of the daily rhythm of gonadotrophins in saline-injected controls and the day of first vaginal discharge was advanced by 4 days compared with saline-injected controls (32.0 +/- 1.8 days vs 36.3 +/- 1.0 days; P less than 0.001). Phenobarbital sodium (100 mg/kg body wt), injected at 13.30 h from 16 to 25 days of age, blocked daily surges of gonadotrophin observed in controls by day 18.(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of precocious puberty in the female rat after chronic naloxone administration during the neonatal period: the opiate 'brake' on prepubertal gonadotrophin secretion

Studies were undertaken using the opiate receptor antagonist naloxone to examine the hypothesis that endogenous opiates may have a restraining effect on prepubertal gonadotrophin secretion and may be involved in the maturation of the central nervous system mechanisms regulating the onset of puberty in the female rat. Naloxone (2.5 mg/kg) administered intraperitoneally every 6 h to female rats from day 1 to day 10 of postnatal life significantly (P less than 0.001) advanced the age of onset of puberty assessed in terms of the day of vaginal opening and first oestrus (32.3 +/- 0.2 vs 40.8 +/- 0.4 days in control saline-treated animals). Animals so treated with naloxone showed significantly (P less than 0.001) higher levels of FSH (761.4 +/- 87.6 vs 483.8 +/- 57.2 micrograms/l in control animals) and LH (562.8 +/- 57.4 vs 351.3 +/- 43.3 micrograms/l in control animals) at the first late pro-oestrus and a significantly (P less than 0.001) higher number of ova released at first oestrus (12.4 +/- 0.4 vs 8.1 +/- 0.3 in controls). Body weight at first oestrus was significantly (P less than 0.001) lower in the naloxone-treated animals, an indication that these animals were much younger. The weights (per 100 g body wt) of the ovaries and uteri at the first oestrus were significantly (P less than 0.01) higher in the naloxone-treated rats than in the controls. However, there were no significant differences in the weights of the adrenals and anterior pituitary glands between the two groups of animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Steroid induction of gonadotropin surges in the immature rat. I. Priming effects of androgens.

Sexually immature female rats were either primed with estradiol benzoate on day 23 or given daily injections of various androgens on days 23--25. Plasma for LH and FSH determinations was collected on day 26, 5 h after an injection of progesterone. Massive gonadotropin surges were found after priming with estradiol benzoate or treatment with dehydroepiandrosterone (DHEA), delta 4-androstenedione, and testosterone, but not with ring A-reduced androgens (5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol, its 3 beta-epimer, and androsterone) or the nonaromatizable 11 beta-hydroxy- and 11-ketoderivatives of delta 4-androstenedione. Rats bearing DHEA-containing Silastic implants also produced LH surges in response to progesterone. A single injection of an antiestrogen antiserum abolished gonadotropin surges in rats primed with estradiol benzoate or DHEA and greatly reduced the accompanying uterine hypertrophy. DHEA and delta 4-androstenedione were barely uterotrophic in ovariectomized rats but sustained progesterone-induced gonadotropin surges. The results indicate that certain (adrenal?) androgens are able to induce maturation of the steroid-sensitive surge system via extragonadal aromatization, whereas their uterotrophic effect is largely mediated by the ovaries. Coordinated increased conversion of androgens at central and peripheral sites may be of physiological importance for the triggering of puberty.     

Attenuation of preovulatory gonadotrophin surges by epostane: a new inhibitor of 3 beta-hydroxysteroid dehydrogenase

Epostane, an inhibitor of 3 beta-hydroxysteroid dehydrogenase, was administered orally to pro-oestrous rats to evaluate further a possible role for preovulatory progesterone secretion in eliciting surges of LH and FSH. Whereas a dose of 10 mg epostane/kg had essentially no effects on preovulatory gonadotrophin surges and ovulation, 200 mg epostane/kg markedly attenuated LH and FSH surges and blocked ovulation. A dose of 50 mg epostane/kg exerted effects on LH and FSH surges and ovulation intermediate between those of doses of 10 and 200 mg/kg. Plasma concentrations of progesterone were significantly lower in all anovulatory epostane-treated rats at 18.00 and 22.00 h on proestrus than those measured in vehicle-treated rats. Concurrent injection of 2 mg progesterone in rats given 200 mg epostane/kg restored gonadotrophin surges to normal, but consistently failed to reverse the inhibitory effects of epostane on ovulation. Peak plasma progesterone levels produced by the progesterone injections were eight- to tenfold higher than the highest levels measured in vehicle-treated rats during the afternoon of pro-oestrus. Insertion of progesterone capsules was less effective than injections of progesterone in restoring gonadotrophin surges to normal, even though peak plasma progesterone concentrations achieved after insertion of two 20 mm long progesterone capsules were double the peak progesterone concentrations measured in control rats. Nevertheless, taken together with recent reports showing attenuation of preovulatory gonadotrophin surges by the progesterone antagonist RU 486 (17 beta-hydroxy-11 beta-[4-dimethyl-aminophenyl]-17 alpha-[prop-1-ynl] estra-4,9-diene-3-one), the present results provide support for a role of preovulatory progesterone secretion in enhancing oestrogen-dependent LH/FSH surges on pro-oestrus.     

Rat placental lactogen-I abolishes nocturnal prolactin surges in the pregnant rat

The twice-daily surges of prolactin (PRL) present during the first half of pregnancy abruptly terminate at midpregnancy concurrent with the appearance of high levels of placental lactogen-I (PL-I) in the blood. This study addressed the role PL-I and other pituitary or placental hormones have in terminating PRL surges in pregnant rats. Implantation of rat PL-I (rPL-I) or ovine PRL into the arcuate-median eminence area of the hypothalamus of day 7 pregnant rats totally eliminated nocturnal PRL surges on days 8 and 9. To assess the specificity of the inhibitory effects of hormones from the PRL-growth hormone (GH) family, rat growth hormone (rGH), human growth hormone (hGH), and rat prolactin-like protein-A (PLP-A) were tested. Only the lactogenic hormone, hGH, had any effect. Since lactogenic hormones may inhibit PRL by stimulation of dopamine synthesis and release into the hypophysial portal blood vessels leading to the anterior pituitary, the effect of these hormones on tyrosine hydroxylase (TH), the rate-limiting enzyme for the synthesis of dopamine activity, was determined. In pregnant rats, both ovine prolactin (oPRL) and hGH significantly increased (64%) TH activity, whereas rPL-I was less effective. In ovariectomized, bromocriptine-treated rats, both rPL-I and oPRL increased TH activity 207 and 151%, respectively. This supports the concept that termination of PRL surges at midpregnancy are owing to secretion of placental lactogens (PLs) from the placenta. However, the mechanism for the inhibition cannot be entirely attributed to an increase in tuberoinfundibular dopaminergic neuronal activity.     

Sex-dependent effect of streptozotocin-induced diabetes mellitus on hepatic steroid metabolism in the rat

Diabetes mellitus is known to affect drug and steroid metabolism in the rat liver. Recently it has been shown that the effect on drug metabolism is both transient and sex-dependent. This study shows that the effect of diabetes on steroid metabolism is also sex-dependent i.e. only seen in the male and the effect is always to abolish the sex differences in steroid metabolism found in the intact animals. 7 alpha-hydroxylase activity, which is higher in the female, is increased by diabetes in the male whereas 6 beta-hydroxylase, 16 alpha-hydroxylase and 17-oxosteroid reductase, which are all higher in the male, are decreased by diabetes. This is a very similar result to that found for drug metabolism and indicates that insulin plays a role in the maintenance of sex differences in hepatic steroid metabolism in the rat as it does for drug metabolism.     

Monosodium L-glutamate administration: effects on gonadotrophin secretion, gonadotrophs and mammotrophs in prepubertal female rats

We have studied gonadotrophin secretion and immunocytochemically stained gonadotrophs and mammotrophs in 35-day-old female rats which had been treated with monosodium glutamate (MSG) as neonates. We also compared our morphometric data in the saline-treated controls with those we have previously obtained in normal adult female rats. The size of the anterior pituitary glands was reduced but the serum levels, the pituitary gland concentrations and contents, and the in-vitro basal release rates of LH and FSH were not significantly altered by MSG treatment. The size of the LH and FSH cells was reduced by MSG administration, but the volume and numerical densities of LH and FSH cells, and the percentage of LH and FSH cells in the pars distalis were not affected. The results suggest that in spite of the smaller size of LH and FSH cells and of the anterior pituitary glands in the MSG-treated rats, the cells contain normal amounts of hormone and the basal LH and FSH secretion rates of the glands are not significantly depressed, contributing to the maintenance of normal serum gonadotrophin concentrations. The volume density of prolactin cells was not increased by MSG treatment. The volume density of gonadotrophs and the percentage of cells which are gonadotrophs in anterior pituitary glands of prepubertal female rats were greater than those in adult female rats, but the reverse was true for the volume density of prolactin cells, suggesting a reciprocal relationship between the relative numbers of gonadotrophs and mammotrophs in prepubertal and adult female rats.     

Binding of human chorionic gonadotrophin to rat ovary during development.

Ovarian tissue of prenatal, newborn, and 5-day-old rats does not specifically bind 125I-labelled HCG. Specific binding of HCG was first observed in ovaries of 10-day-old animals and binding increased with age. These results indicate that, contrary to rat testis, the HCG receptor in the rat ovary is not present during foetal and early postnatal development. Thus, the insensitivity of the ovary to endogenous and exogenous LH or HCG during this developmental period is due to the lack of specific receptors.     

A histochemical approach to the study of human chorionic gonadotrophin receptors in the rat testis.

Standard suspensions of interstitial cells in PBS were exposed to the action of various fixatives, solvents (clearing agents), temperatures and U. V. light, in order to establish the effects of such chemical and physical agents on the HCG receptors. After exposure to the various agents, the interstitial cells were incubated with [125I]HCG for 2 h at 37 degrees C. To check the specificity of the reaction, competitive tests were performed with added excess non-iodinated HCG. Only formaldehyde fixation for short periods of time, preserved satisfactorily the specific binding activity of the receptors. A different degree of thermolability of the receptors was demonstrated, in relation to 37, 45, 54 and 60 degrees C, while freezing in liquid nitrogen had no effect on the receptors binding activity. After the binding reaction, solvents had a significant solubilizing effect on the HCG-receptor complexes. U. V. light had no significant damaging effect on the receptors. The application of the results for a histochemical approach to the study of the HCG receptors is discussed.