Publisher Summary This chapter reviews the historical perspective into the conceptual evolution of 11β-hydroxysteroid dehydrogenase (HSD) from its pedestrian origin as an enzyme that catalyzes reversible inactivation of corticosteroids to its currently more prestigious role as mediator of steroid-receptor interactions An enzyme responsible for catalyzing the oxidation of cortisol to cortisone is found in rat liver and named “l lβ-hydroxy dehydrogenase” The transformations catalyzed by this enzyme are illustrated in the chapter The catalysis of 11-oxidation and 11-oxoreduction is not uniformly distributed among tissues In liver, 11-oxoreduction is the dominant activity; in most other tissues, it is 11β-hydroxy oxidation The recognition of clinical disorders whose symptomatology could be rationalized as being because of defects in 11-HSD expression It helps in the development of the tools—antibodies, complementary DNA (cDNA)—that facilitate exploration of the enzyme at the molecular level 11-HSD protects cells against the toxic effects of excess corticosteroid The enzyme also serves a conservationist function, as the oxidized form of the steroid can be reduced by 11-oxoreductase to its active reduced form thus contributing to the circulating cortisol, and providing a buffer against the changes in blood level caused by paroxysmal secretion of the adrenal

11 beta-hydroxysteroid dehydrogenase.

Molecular studies of corticosteroid binding globulin structure, biosynthesis and function.

We have recently demonstrated that the rates of both active and passive proximal straight tubule (PST) NaCl transport in neonatal rabbits were less than in adults. In this segment NaCl entry across...

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Maturation of proximal straight tubule NaCl transport: role of thyroid hormone

The sections in this article are:


1
Ontogeny of the Hypothalamic-Pituitary-Adrenal Axis
11
Hypothalamic Paraventricular Nucleus

12
Pituitary Function

13
Adrenal Function

14
Glucocorticoid Feedback

15
Hypothalamic-Pituitary-Adrenal Function and Stress Responsiveness in Development




2
Conclusions

Development of the Hypothalamic‐Pituitary‐Adrenal Axis and the Stress Response

The cDNA-deduced primary structure of rabbit corticosteroid- binding globulin (CBG) contains 383 amino acids (mol wt, 42,326), including three cysteine residues and four sites for N-glycosylation. It is primarily the product of a 1.68-kilobase hepatic mRNA, but small amounts of CBG mRNA were also found in maternal lung, spleen, and ovary and fetal kidney. In the fetus, hepatic CBG mRNA concentrations increase markedly after day 11 and were 2- to 5-fold higher than those in maternal liver during days 17–23. They then declined to very low levels at term (31 days). By contrast, maternal hepatic CBG mRNA levels did not increase until day 23; reached a peak at about day 27, and then declined to prepregnancy values by 3 days after delivery. In general, fetal and maternal hepatic CBG mRNA concentrations reflect the corresponding serum CBG levels. Our data, therefore, indicate that the marked changes in fetal and maternal plasma CBG levels during pregnancy reflect changes in the biosynthesis of the protein rather...

Rabbit Corticosteroid-Binding Globulin: Primary Structure and Biosynthesis during Pregnancy

Corticosteroid treatment of the fetus, which accelerates lung maturation, may mimic a modulating role of endogenous corticoids in normal development. To investigate this question, we determined the developmental pattern of plasma corticoids and their binding proteins in the rabbit, a commonly used species for studies of lung differentiation. The concentration of cortisol, the most potent glucocorticoid in the rabbit, was maximal at 23 days gestation (1.89 μg/dl), declining to 0.54 μg/dl at term (31 days). Levels of plasma corticosterone were always lower than those of cortisol. The adrenal content of corticoids, expressed per adrenal DNA or g BW, decreased during late gestation. Corticosteroid-binding globulin in fetal plasma decreased strikingly between day 23 (36 fig cortisol bound/dl) and day 31 (4.4 μg/dl; P < 0.001), whereas maternal levels increased about 10-fold during this time. Free cortisol in the fetus increased between 21 and 23 days (0.041 μg/dl) and then decreased somewhat until after day 29...

Raimund Hummelink

Papers

Endogenous corticoids and lung development in the fetal rabbit.