ABSTRACT

In this study, aimed at investigating whether dopaminergic regulation of prolactin could be implicated in the hypoprolactinaemia observed in the IPL nude rat, dopaminergic inhibition of prolactin was suppressed using a catecholamine synthesis inhibitor α-methyltyrosine (MT) and a dopaminergic antagonist sulpiride.

Adult male rats (IPL nude and normal) were injected through implanted atrial cannulae with either MT (250 mg/kg) or physiological saline (control). Rats were decapitated 2 h after the injection. Plasma prolactin levels, compared with basal values, increased by 15·6 ± 1·9 (s.e.m.)- and 5·89 ± 0·6-fold in IPL nude and normal rats respectively. This difference was highly significant. The pituitary prolactin content was decreased in both groups.

In a second experiment, adult male IPL nude or normal rats were injected with either sulpiride (1 mg/kg) or saline and decapitated 2, 4, 8, 12, 14 and 24 h later. Plasma prolactin levels, compared with basal values, were increased in rats injected with sulpiride by 9·2 ± 1·8 and 3·4 ± 0·7-fold in IPL nude and normal rats respectively. The pituitary prolactin content was reduced more in IPL nude than in normal sulpiride-injected rats. These data suggest that prolactin secretion, as well as synthesis, is under an increased dopaminergic inhibition in the male IPL nude rat.

J. Endocr. (1985) 107, 325–329

In ewes, photoperiod modulates LH release and dopaminergic terminals in the median eminence (ME) have a critical role in the establishment of long-day inhibition of LH secretion. This study was undertaken to determine the type of dopaminergic receptors, D1-like or D2-like, that mediate the action of dopamine on LH secretion at the ME level in this situation. This was assessed, in ovariectomized and estradiol-treated ewes, with the use of reverse microdialysis in the ME in three experiments: first, when LH secretion was stimulated by short days, by determining the response to three doses (0.01, 0.1 or 1 mg/ml) of a D1-like (SKF38393) and a D2-like (quinpirole) agonist; secondly, during early long-day inhibition of LH secretion, by determining the ability of SKF38393 and quinpirole (1 mg/ml) to mimic the inhibitory effects of dopamine, after a blockade of its synthesis with alpha-methyl-para-tyrosine (alphaMPT; 2 mg/ml); and thirdly, during early long-day inhibition of LH secretion, by determining the response to three doses (0.009, 0.09 or 0.9 mg/ml) of a D1-like (SCH23390) and a D2-like (sulpiride) antagonist. In none of the conditions was effect of the D1-like analogs on LH secretion found, compared with the control treatments. In contrast, the D2-like analogs caused changes in LH secretion. First, with short days, quinpirole in the highest dose significantly reduced mean LH concentration (P<0.05) and LH pulse frequency (P<0.01). Secondly, with long days, addition of quinpirole to alphaMPT caused a significant decrease in LH secretion relative to alphaMPT alone (P<0.05). Thirdly, with long days, sulpiride at the highest dose significantly increased mean LH concentration (during the first 3 h of treatment, P<0.05) and LH pulse frequency (P<0.05). Prolactin secretion was also determined in these experiments, and D2-like agonist and antagonist caused an inhibition and a stimulation of prolactin secretion, respectively. These results demonstrate that, in the ME, inhibitory action of dopamine on LH secretion, critical for the initiation of long-day-induced inhibition, is mediated by D2-like, not D1-like, dopaminergic receptors.

SUMMARY

Plasma levels of testosterone, androst-4-ene-3,17-dione, dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulphate (DHAS) were estimated both before and after administration of clomiphene citrate to endocrinologically normal boys aged from 2–16 yr and to boys with adrenocortical hypofunction or hypogonadism. A divided daily dose of 200 mg/1·7 m² of surface area was maintained for 15 days. The unconjugated steroids were measured by means of a double isotope derivative technique and the sulphates by gas-liquid chromatography.

The boys without testicular anomaly who were well established in puberty responded with a rise in plasma testosterone. In contrast, prepubertal boys showed a statistically significant decrease in plasma testosterone levels.

A concomitant finding was a significant rise in the plasma levels of androstenedione, DHA and DHAS. It is concluded that clomiphene does not liberate luteinizing hormone before puberty but it may well diminish its secretion. A secondary effect of clomiphene is the stimulation of adrenal C₁₉-steroid production.

SUMMARY

Eight women with secondary amenorrhoea were treated, four at each of two centres. They were each given four preparations of gonadotrophin having different ratios of follicle-stimulating hormone (FSH) to luteinizing hormone (LH) and the order of treatment with the preparations was determined at each centre by a latin square design. At the completion of these treatments each patient received a fifth preparation of gonadotrophin. The dosage of FSH was determined for each woman by a previous sensitivity test and remained constant for each of her 5 months of treatment. Each gonadotrophin preparation was given in approximately equal daily injections on days 1, 2 and 3 of each course of treatment and was invariably followed by a single injection of 12000 i.u. human chorionic gonadotrophin on the 10th day. Treatment was assessed by the measurement of the excretion of oestriol and pregnanediol, by vaginal cytology, by the degree of ferning of cervical mucus and by the basal body temperature (BBT). The administration of gonadotrophin with a ratio of FSH:LH < 1·0 produced a greater excretion of oestriol than gonadotrophin with a ratio of FSH:LH > 4·0. There was no significant loss of sensitivity to treatment with time. The karyopyknotic index was correlated with the excretion of oestriol but neither was of use in predicting the other because of the wide scatter. There was no correlation between the degree of ferning and the excretion of oestriol. Assessments of ovulation by the pregnanediol response and by the BBT were in good agreement. These results are discussed.