Cell Biology of Leydig Cells in the Testis

Key factors in the regulation of fetal and postnatal leydig cell development

“…In the Tfm mice, which lack functional androgen receptors, androgen production by fetal Leydig cells appears to be enhanced in that P450c17, a key enzyme in sex hormone biosynthesis, is higher on postnatal Day 5 (Murphy et al, 1994). This may be due to lack of negative feedback through the hypothalamic-pituitary-gonadal axis rather than a direct effect as fetal Leydig cells do not express androgen receptor and their androgen steroidogenesis is not affected by anti-androgens (Haider, 2004). Fetal Leydig cells have also been shown to be insensitive to the inhibitory effects of estrogens, a property which would enable the fetus to circumvent the higher concentrations of maternal estrogens that are present in the intra-uterine milieu (Huhtaniemi and Pelliniemi, 1992).…”

“…As the testis organizes into cords at 13.5 dpc in rats, 3b-hydroxysteroid dehydrogenase (3b-HSD) starts to be expressed in somatic interstitial cells. By 15.5 dpc, these cells are identifiable as fetal Leydig cells by ultrastructural features that are characteristic of steroidogenic cells (Haider, 2004). During the critical window of sexual differentiation, the abundant production of testosterone and conversion to its more active metabolite, dihydrotestosterone, are gonadotropin independent (Huhtaniemi and Pelliniemi, 1992).…”

“…Commitment to the Leydig cell lineage is noted by the onset of expression of enzymes in the steroidogenic pathway as the proliferating mesenchymal stem cells differentiate to PLCs (Shan and Hardy, 1992). The adult PLCs start to differentiate in the second postnatal week in response to LH, IGF-1, and other stimulatory factors (Ge et al, 1996;Habert et al, 2001;Haider, 2004). The PLCs continue to proliferate but their mitotic activity is tempered by the inhibitory influences of Mullerian inhibiting substance and estradiol (Lee, 2000;MendisHandagama and Ariyaratne, 2001;Wu et al, 2005).…”

“…The proliferation of precursor Leydig cells increases after treatment with exogenous LH or human chorionic gonadotropin Haider, 2004). However, LH is not considered an essential mitogen for mesenchymal stem cells or for initial Leydig cell differentiation, as supported by several lines of evidence.…”

“…The studies on models of hypo-and hyper-thyroidism in rodents suggest that thyroid hormone appears to inhibit the proliferation of mesenchymal cell precursors and stimulate their differentiation into progenitor and more mature Leydig cells Habert et al, 2001;Haider, 2004). Some of the discrepant data on thyroid hormone actions may be due to the profound effects of thyroid hormone on the Sertoli cell compartment, thus the effects of manipulating thyroid status may cause both direct effects on the Leydig cells and indirect paracrine effects through Sertoli cells.…”