Blockade of the hypothalamic-pituitary-testicular axis with a GnRH antagonist in the neonatal marmoset monkey:...

Little is known of the cell biology of Leydig cells during the neonatal activation of the hypothalamic-pituitary-testicular (HPT) axis. The current study examined the effect of blockade of the HPT axis with a GnRH antagonist (antide) on the neonatal population of Leydig cells in the new world primate, the common marmoset. Three sets of twins, age 7 weeks, were studied: in each pair one twin was used as a control, while the other received treatment with GnRH antagonist from the day of birth to suppress pituitary gonadotrophin secretion. Leydig cells of treated animals were dramatically different from those of controls. The cells were atrophic and exhibited very irregular nuclei. The organelles involved in steroid synthesis were reduced to the extent to being barely evident. The smooth endoplasmic reticulum (SER) was greatly diminished in quantity and distribution. The usual form of the SER (anastomosing tubules) was not evident, but, instead, the SER was relatively unbranched. Peroxisomes, organelles involved in transfer of cholesterol to the mitochondria, were greatly reduced in number. Mitochondria were relatively sparse and exhibited a non-typical morphology, as tubular elements of the cristae were rarely evident. Thus, the central apparatus in steroid production, the SER, mitochondria and peroxisomes, was essentially shut down in the GnRH-antagonist-treated animals. Storage of cholesterol, the precursor of steroid biosynthesis, was also not in evidence, as lipid droplets were extremely rare. Two prominent features of control in neonatal marmoset Leydig cells, the membranofibrillar inclusion (MFI) and basal laminae, remain prominent in the Leydig cells of treated animals. Evidence of apoptosis was not observed. These results provide strong support that the gonadotrophic hormones are the primary regulator of neonatal Leydig cell development in primates, and also suggest cell regression, rather than apoptosis, being the mechanism of this inhibition.