CAMP DEPENDENT TRANSCRIPTIONAL REGULATION OF CYP51

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The long term goal of collaborative research between the P.I. and the foreign collaborator is to determine the role of the high level expression of CYP51 (lanosterol 14alpha-demethylase cytochrome P450) in haploid, postmeiotic germ cells. This FIRCA proposal addresses a portion of this overall goal and will lead to an understanding of the biochemical mechanisms involved in cAMP-dependent transcription of CYP51 in somatic and germ cells. The specific aims for the proposed three years are to study cAMP- dependent transcriptional regulation of CYP51 in steroidogenic (somatic) cells (Aim 1) and in haploid germ cells (Aim 2). The parent grant (DK28350) addresses ACTH (cAMP)-dependent transcription of genes (particularly encoding P450 enzymes) in the adrenal cortex, a process essential for maintenance of optimal steroidogenic capacity. Aim 1 is an extension of DK28350 and will establish whether a link between cAMP-dependent transcription of genes encoding steroidogenic P450s (cholesterol metabolism) and CYP51 (cholesterol biosynthesis) exists in the adrenal cortex. It seems likely that two different signalling pathways, oxysterol/SRE and cAMP/CRE, interact to control CYP51 levels in steroidogenic cells. Preliminary data indicates that CYP51 is transcriptionally regulated by cAMP in haploid germ cells. Aim 2 is a new direction for studies in DK28350 and will establish the biochemical basis of this postmeiotic transcriptional regulation. Results from these studies will provide a more detailed understanding of steroid hormone biosynthesis which is a major path of cholesterol metabolism and of spermatogenesis in male reproduction.