LH was detectable initially in the fetal pituitary gland on E16.5, and in the fetal plasma at very low levels (< 0.005 (xg/L) on E17.5. The first significant increase in this level was delayed until E20.5, which corresponds to the age when the pituitary LH has been found to start stimulating fetal Leydig cell steroidogenesis in rats . However, when testicular testosterone contents were measured, a totally different pattern appeared. Surprisingly, the sharpest increase occurred between Days E18.5 and E19.5, when no significant level of LH could be detected in the fetal circulation. After E19.5, there was a decline in testicular testosterone that occurred simultaneously with an increase in plasma LH. Our finding that the greatest increase in fetal testicular steroidogenesis is attained before any significant level of LH could be detected in the fetal circulation implies that fetal testicular steroidogenesis initially does not require LH stimulation. The early phase of this activity is therefore either autonomous or regulated by other paracrine or endocrine factors, and the dependence on gonadotropins is only acquired later. buy asthma inhaler
There are several pieces of evidence in line with the above finding, suggesting the independence of the initial phase of fetal testicular steroidogenesis on pituitary gonadotropins. Male hpg mice, with an inactivating deletion mutation of the GnRH gene, and consequently low gonadotropin levels, display complete androgen-dependent sexual differentiation at birth . Likewise, the gonadotropin-deficient mouse with targeted disruption of the common a-subunit gene is normally masculinized at birth . To support the gonadotropin independence, we found that a low level of recombinant LH (0.025 (ig/L of RP-2, about 5-fold higher than plasma LH on Day E17.5) could not stimulate fetal testosterone production. The presence in the fetal testis of an alternate form of LH receptor that can be activated without ligand is also possible in view of the multiple forms of LH receptor mRNA , some of which could encode for structurally and/or functionally different receptor proteins. However, as demonstrated by the present data, there are other hormones and growth factors that may be responsible for the LH-independent function of fetal Leydig cells.