Publisher Summary Congenital adrenal hyperplasia (CAH) is a family of disorders of adrenal steroidogenesis resulting from an inherited deficiency of one of several enzymes necessary for normal steroid synthesis. This chapter describes the recent advances in congenital adrenal hyperplasia. These advances have come from the interdisciplinary collaboration of embryologists, teratologists, enzymologists, immunogeneticists, population geneticists, steroid endocrinologists, and gender psychologists. The chapter describes asimplified scheme of adrenal steroidogenesis. It provides an overview of the additional evidence that supports the concept that the adrenal fasciculate and glomerulosa function as two separate glands. This has been gained from the recent study of patients with 21-hydroxylase deficiency. New data shows that in CAH, there is a 21-hydroxylation defect in the zona fasciculata of simple virilizers and salt wasters, whereas zona glomerulosa is defective in salt wasters and not in simple virilizers. The data suggest that there is one enzyme involved in the 21-hydroxylation of the 17-hydroxy and 17-deoxy pathways of adrenal steroidogenesis in zona fasciculata.

An Update of Congenital Adrenal Hyperplasia

Male pseudohermaphroditism: the complexities of male phenotypic development.

Publisher Summary This chapter discusses the aspects of ovarian cholesterol metabolism that appear to be subject to control, directly or indirectly, by gonadotropins. These include lipoprotein uptake, de novo sterol synthesis, intracellular cholesterol transport, mitochondrial cholesterol side chain cleavage, and the synthesis and hydrolysis of cholesteryl esters. The chapter focuses on the corpus luteum as this is the best studied component of the ovary with respect to sterol metabolism. Luteal cells have a unique life cycle; their steroidogenic activity and, therefore, their cholesterol requirements change dramatically as they differentiate from granulosa cells and undergo a period of secretory activity followed by a phase of waning function and structural demise.

Cholesterol metabolism by ovarian tissue.

Adrenocortical mitochondrial cholesterol side chain cleavage reactions are regulated by the influence of pituitary ACTH. The mechanism of the stimulation involves adenyl cyclase, cAMP-dependent protein kinase, cholesterol esterase, and ribosomal labile protein synthesis. Through these reactions the stimulus reaches the mitochondrial side chain cleavage enzyme system. In this review article, the current implications on the stimulus transfer from the plasma membrane to the mitochondrial inner membrane are summarized. In particular the availability of cholesterol to P-450scc was discussed in terms of the distribution of cholesterol molecules in the membranes.

ACTH stimulation on cholesterol side chain cleavage activity of adrenocortical mitochondria. Transfer of the stimulus from plasma membrane to mitochondria.

http://www.jbc.org/content/250/23/9028.full.pdf

Mass spectrometric study of the enzymatic conversion of cholesterol to (22R)-22-hydroxycholesterol, (20R,22R)-20,22-dihydroxycholesterol, and pregnenolone, and of (22R)-22-hydroxycholesterol to the lgycol and pregnenolone in bovine adrenocortical preparations. Mode of oxygen incorporation.

https://www.jbc.org/content/247/5/1462.full.pdf

Studies on the Biosynthetic Conversion of Cholesterol into Pregnenolone SIDE CHAIN CLEAVAGE OF A t-BUTYL ANALOG OF 20α-HYDROXYCHOLESTEROL, (20R)-20-t-BUTYL-5PREGNENE-3β,20-DIOL, A COMPOUND COMPLETELY SUBSTITUTED AT C-22

Brian Luttrell

Papers

Studies on the Biosynthetic Conversion of Cholesterol into Pregnenolone SIDE CHAIN CLEAVAGE OF A t-BUTYL ANALOG OF 20α-HYDROXYCHOLESTEROL, (20R)-20-t-BUTYL-5PREGNENE-3β,20-DIOL, A COMPOUND COMPLETELY SUBSTITUTED AT C-22