Blockade of the hypothalamic-pituitary-testicular axis with a GnRH antagonist in the neonatal marmoset monkey: changes in Leydig cell ultrastructure

Little is known of the cell biology of Leydig cells during the neonatal act ivation of the hypothalamic-pituitary-testicular (HPT) axis. The current st udy 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 primat e, 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 treatmen t with GnRH antagonist from the day of birth to suppress pituitary gonadotr ophin secretion. Leydig cells of treated animals were dramatically differen t from those of controls. The cells were atrophic and exhibited very irregu lar nuclei. The organelles involved in steroid synthesis were reduced to th e extent of being barely evident. The smooth endoplasmic reticulum (SER) wa s greatly diminished in quantity and distribution. The usual form of the SE R (anastomosing tubules) was not evident, but, instead, the SER was relativ ely unbranched. Peroxisomes, organelles involved in transfer of cholesterol to the mitochondria, were greatly reduced in number. Mitochondria were rel atively 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 dow n in the GnRH-antagonist-treated animals. Storage of cholesterol, the precu rsor of steroid biosynthesis, was also not in evidence, as lipid droplets w ere extremely rare. Two prominent features of control in neonatal marmoset Leydig cells, the membranofibrillar inclusion (MFI) and basal laminae, rema in prominent in the Leydig cells of treated animals. Evidence of apoptosis was not observed. These results provide strong support that the gonadotroph ic hormones are the primary regulator of neonatal Leydig cell development i n primates, and also suggest cell regression, rather than apoptosis, being the mechanism of this inhibition.