ABSTRACT

Orchidectomy has been reported to decrease concentrations of thyrotrophin (TSH) in the circulation of male rats without affecting serum levels of thyroid hormones. To understand the mechanism underlying this observation, we have measured the effect of gonadal status on the in-vitro release of TSH-releasing hormone (TRH) by male rat hypothalamic fragments. Because hormone release rates can be affected by changes in the post-translational processing of the hormonal precursors, we have also studied the corresponding changes in the concentrations of TRH and TRH-Gly, a TRH precursor peptide in hypothalamus and pituitary, by radioimmunoassay.

We observed a significant decline in the in-vitro release of TRH from incubated hypothalami 1 week after castration, which was quantitatively reversed by testosterone replacement. Concentrations of TRH and TRH-Gly in the posterior pituitary, on the other hand, which derive from neurones of hypothalamic origin, increased significantly with castration and were returned to the normal range by testosterone replacement.

We conclude that the primary effect of testosterone is the stimulation of hypothalamic TRH release, resulting in the depletion of TRH and TRH precursors from TRH-containing neurones which project into the median eminence and posterior pituitary.

Journal of Endocrinology (1990) 125, 263–270

Endogenous glucocorticoid action is important in the structural and functional maturation of the fetal heart. In fetal mice, although glucocorticoid concentrations are extremely low before E14.5, glucocorticoid receptor (GR) is expressed in the heart from E10.5. To investigate whether activation of cardiac GR prior to E14.5 induces precocious fetal heart maturation, we administered dexamethasone in the drinking water of pregnant dams from E12.5 to E15.5. To test the direct effects of glucocorticoids upon the cardiovascular system we used SMGRKO mice, with Sm22-Cre-mediated disruption of GR in cardiomyocytes and vascular smooth muscle. Contrary to expectations, echocardiography showed no advancement of functional maturation of the fetal heart. Moreover, litter size was decreased 2 days following cessation of antenatal glucocorticoid exposure, irrespective of fetal genotype. The myocardial performance index and E/A wave ratio, markers of fetal heart maturation, were not significantly affected by dexamethasone treatment in either genotype. Dexamethasone treatment transiently decreased the myocardial deceleration index (MDI; a marker of diastolic function), in control fetuses at E15.5, with recovery by E17.5, 2 days after cessation of treatment. MDI was lower in SMGRKO than in control fetuses and was unaffected by dexamethasone. The transient decrease in MDI was associated with repression of cardiac GR in control fetuses following dexamethasone treatment. Measurement of glucocorticoid levels in fetal tissue and hypothalamic corticotropin-releasing hormone (Crh) mRNA levels suggest complex and differential effects of dexamethasone treatment upon the hypothalamic–pituitary–adrenal axis between genotypes. These data suggest potentially detrimental and direct effects of antenatal glucocorticoid treatment upon fetal heart function.