Area:
Epithelial sodium channel (ENaC), Steroidogenesis, Keratin structure, Oxidoreductase enzymes, Cell biology
Website:
https://www.science.co.il/hi/
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High-probability grants
According to our matching algorithm, Israel Hanukoglu is the likely recipient of the following grants.
| Years |
Recipients |
Code |
Title / Keywords |
Matching
score |
| 1985 — 1986 |
Hanukoglu, Israel |
R01Activity Code Description:
To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Molecular Genetics of Steroid Hydroxylase Systems @ Technion-Israel Institute of Technology
In mammals, steroid hormones represent some of the most important agents that coordinate the physiological functions of the body in adult life and also during pregnancy and early development. These hormones are synthesized mainly in four endocrine tissues: the adrenal cortex, the ovary, the testis and the placenta. The steroid output of these tissues is regulated by tissue specific peptide hormones that control the levels of the enzymes that catalyze steroid biosynthesis. The objectives of our research are to elucidate the mechanisms by which the peptide hormones regulate the expression of the genes that code for these enzymes, and to identify the locus and nature of the biochemical defects in congenital adrenal hyperplasias (CAH) which are known to emanate from specific errors in steroid biosynthesis. In all steroidogenic tissues, the majority of the steps in the biosynthesis of steroid hormones are catalyzed by monooxygenase enzymes called cytochromes P-450 which represent a large family of related proteins. Therefore, as the initial step towards the major objectives of this proposal it is essential to isolate and characterize the genes that encode these proteins. For this purpose, we shall develop libraries of cloned cDNAs that represent copies of mRNAs in bovine steroidogenic tissues and identify among these the clones that code for the major mitochondrial and microsomal steroidogenic monooxygenase enzymes, especially, cytochrome P-450scc specific for cholesterol side chain cleavage, and P-450C-21' specific for 21-hydroxylation in the adrenal cortex. The sequences of these cloned cDNAs will be compared to determine whether the enzymes that carry homologous reactions in different tissues are the products of the same or different genes. The amino acid sequences that will be predicted from the cDNA sequences will establish the structural relationships of these enzyme. With these studies and additional Southern blot analyses of genomic DNA, the number of genes that code for these enzymes will be estimated. Using the cloned cDNAs as probes the location of these genes on human metaphase chromosomes will be determined by in situ hybridizations. Comparison of the chromosomal maps with previous genetic analyses should indicate whether CAH due to 21 hydroxylase deficiency is a result of a genetic defect in the structural gene for the enzyme or a different gene. Human genomic sequences coding for these genes will be isolated to further define the molecular basis of this disease. The cloned cDNAs will prove invaluable in future investigations of these genes.
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