Testosterone production in human males has been shown biochemically to be elevated during early fetal life, neonatally and from puberty onward. These phases of testosterone secretion are instrumental in a sequential development of male characteristics, such as the reproductive tract during fetal life, hypothalamic differentiation (with physiological and behavioral implications) and the male pubertal maturation. Surprisingly, the phases of morphological development of this system have not been elucidated. The morphometric techniques of Weibel will be employed, both at the histologic and ultranstructural levels, to quantify the changes in the testicular interstitium from the neonatal period through puberty. Previously obtained humans specimens (age 4 months to 19 years) will be utlized in this regard. Major questions to be addressed will be: (1) What is the cellularity present neonatally, when testosterone levels are high? (2) Do the neonatal cells degenerate or regress? (3) What is the source of the pubertal development of Leydig cells? A previous paper by this investigator has demonstrated the presence of cells exhibiting a steroid-producing morphology (immature Leydig cells) during the long prepubertal period in humans. (4) What quantitative changes in the organelles involved with steroid biosynthesis are found in the transition from the immature Leydig cells of childhood to the mature adult Leydig cell? A clear description of the phases of cellular differentiation which the human Leydig cells undergo is essential for understanding the basic development of the male system as well as a myriad of medically related subjects (for example: cryptorchidism, infertility, interrelationships of Leydig cells with the tubules, effects of exogenous androgens in the testis, to name a few). The purpose of this project is to elucidate this morphological development of the androgen-secreting Leydig cells of the testicular interstitium in humans during the period from shortly after birth until pubertal maturation.
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