Thyroid and Anti-Mullerian Hormones on Leydig Stem Cell Differentiation

Androgens are essential to the male mammal for the general health and reproductive functions; Leydig cells in the testis interstitium are their main source. Therefore, the establishment of the adult Leydig cell population in the postnatal testis is an important event in the mammalian male, where the process begins during the prepubertal life. It is established that the adult population of Leydig cells is differentiated primarily from the peritubular mesenchymal cells in the testis. Five distinct cell stages, namely the mesenchymal cells {i.e. stem cells), progenitor cells, newly formed adult Leydig cells, immature Leydig cells and mature Leydig cells are identified in the Leydig ceil lineage. At the onset of Leydig cell differentiation in the postnatal testis, a mesenchymal cell which is non-steroidogenic, differentiates into a progenitor cell which is still similar in shape to a mesenchymal cell but contains some steroidogenic enzymes. The trigger mechanism of this process is yet to be determined. Recent research has shown that this differentiation process is arrested under hypothyroid conditions and accelerated with hyperthyroid conditions. These findings suggest that thyroid hormones have a positive regulatory role in this process. Nevertheless, anti-Mullerian hormone (AMH) secreted by the immature Sertoli cells is considered to be a negative regulator of Leydig cell differentiation. Thyroid hormones and AMH could act directly on the mesenchymal precursor cells to trigger and inhibit, respectively, the process of Leydig cell differentiation. Additionally, thyroid hormones could act on Sertoli cells to induce maturation and inhibit the AMH production; this withdrawal of the inhibitory effect of AMH could possibly trigger the onset of mesenchymal cell differentiation. These concepts were addressed in this paper using evidence from experiments conducted in rats.