Stephanie Fritz

Determination of cDNA, gene structure and chromosomal localization of the novel human 17β‐hydroxysteroid dehydrogenase type 7

We have identified human 17β‐hydroxysteroid dehydrogenase type 7 (17β‐HSD 7). The novel human cDNA encodes a 37 kDa protein that shows 78 and 74% amino acid identity with rat and mouse 17β‐HSD 7, respectively. These enzymes are responsible for estradiol production in the corpus luteum during pregnancy, but are also present in placenta and several steroid target tissues (breast, testis and prostate) as revealed by RT‐PCR. The human 17β‐HSD 7 gene (HSD17B7) consists of nine exons and eight introns, spanning 21.8 kb and maps to chromosome 10p11.2 close to susceptibility loci for tumor progression, obesity and diabetes. The HSD17B7 promoter (1.2 kb) reveals binding sites for brain‐specific and lymphoid transcription factors corresponding to additional expression domains in hematopoietic tissues and the developing brain as identified by in silico Northern blot.

StAR protein is increased by muscarinic receptor activation in human luteinized granulosa cells.

Cultured human luteinized granulosa cells (GC) are a unique model to study regulation of the human corpus luteum, e.g. by local factors, including acetylcholine (ACh). GC express functional ACh-receptors of the M1-type (M1R). Priming with the cholinergic agonist carbachol for 24 h, followed by a 24 h stimulation with human chorionic gonadotrophin (hCG), significantly increased progesterone levels (up to 2-fold), compared with hCG stimulation alone. This is likely due to the effect of carbachol, observed after 24 h, to increase the levels of steroid acute regulatory (StAR) protein, as found in Western blots. StAR protein was increased (2-10-fold), while P450 side chain cleavage (SCC) enzyme was unaffected. Thus, one role of muscarinic receptor activation in human GC is regulation of StAR protein and, subsequently, progesterone production.