**4. References**


insulin because there were no reports of serum insulin measurements in guinea pigs (Massey&Smyth,1975; Rosenzweig et al.,1980; Gracia-Webb et al.,1983; Schlosser et al.,1987). Guinea pigs in the IGT group showed a significant decrease in serum c-peptide levels and it was speculated that this was not hyper-insulinemia. In IGT group guinea pigs, blood glucose levels improved after DHEA-S administration, however serum c-peptide levels were still significantly decreased. There was no correlation between serum c-peptide levels and DHEA or DHEA-S levels. In the STZ-induced model of diabetes, adult rats ranged from mild type 2 diabetes to type 1 diabetes depending upon STZ dose (Ho RS et al.,1988). In this experiment, fasting blood glucose levels in STZ-administered guinea pigs were not significantly different from those in control group. However, serum c-peptide levels were

Similar to clinical data, it was thought that hyperglycemia itself suppressed DHEA and DHEA-S after prolonged hyperglycemia independent of serum insulin levels in the absence of hyperinsulinemia. In IGT group guinea pigs, serum c-peptide was still decreased after DHEA-S administration, however blood glucose levels improved significantly. It was thought that DHEA-S itself was involved in this improvement of blood glucose levels. In the hyperglycemic state in humans, the mechanism of decrease of DHEA and DHEA-S levels is not still clear. It has been reported that DHEA levels are low in situations of life-threatening stress(Parker et al., 1985; Wade et al.,1988). Long duration hyperglycemia in this experiment is a form of excessive stress. It was speculated that histological changes in the adrenal gland may occur. The zona fasciculata which secretes cortisol necessary to maintain life may become enlarged and the zona reticularis which secretes DHEA and DHEA-S may shrink. In addition to reports of the mechanism of the improvement of impaired glucose tolerance by DHEA and DHEA-S, further studies reported a number of other effects. These included acceleration of glucose uptake in cells, increasing sensitivity in insulin sensitive tissue and suppressing the activities of G6Pase and FBPase, the enzymes of glyconeogenesis in the liver(McIntosh & Berdanier,1991; Nakashima et al.,1995) However, many points remained

These experiments suggest that the relationship between blood glucose levels and DHEA or DHEA-S is close. It is therefore possible that DHEA-S may become a therapeutic agent for

Barrett-Connor, E. (1992). Lower endogenous androben levels and dyslipidemia in men with non-insulin-dependent diabetes mellitus. *Annals of Internal Medicine,* 117, 807-811. Cleary, MP. (1991). The antiobesity effect of dehydroepiandrosterone in rats. *Proc Soc Exp* 

Coleman, DL. Leiter, EH. Schwizer, RW. (1982). Therapeutic effects of dehydroepiandrosterone

Couch, RM. (1992). Dissociation of cortisol and adrenal androgen secretion in poorly controlled insulin-dependent diabetes mellitus. *Acta Endocrinologica*, 127, 115-117. Farah, MJ. Givens, JR. Kitabchi, AE. (1992). Bimodel correlation between the circulating

insulin level and the production rate of dehydroepiandrosterone: Positive

decreased and this state was thought to be approaching type 1 diabetes.

unclear.

**3. Conclusion** 

**4. References** 

diabetes mellitus in the future.

*Biol Med*, 196, 8-16.

(DHEA) in diabetic mice. *Diabetes,* 31, 830-833.

correlation in controls and negative correlation in the polycystic ovary syndrome with acanthosis nigricans. *Journal of Clinical Endocrinology and Metabolism,* 70, 1075- 1081.


**7** 

*Italy* 

**17β-Hydroxysteroid Dehydrogenase** 

*Department of Biomedicine of Developmental Age, University of Bari,* 

**Variability and Molecular Findings** 

Maria Felicia Faienza and Luciano Cavallo

**Type 3 Deficiency: Diagnosis, Phenotypic** 

The steroid hormones are lipophilic compounds with low molecular weight, derived from cholesterol, which play a crucial role in differentiation, development and physiological functions of many tissues. They are synthesized primarily by endocrine glands, such as the gonads, the adrenal glands and the feto-placental unit during pregnancy. In addition, the central nervous system (CNS) seems to be able to synthesize a number of biologically active steroids, termed "neurosteroids", with autocrine or paracrine functions (Baulieu, 1991). The circulating steroid hormones act both on peripheral target tissues and on the CNS, coordinating physiological and behavioral responses with specific biological purposes, e.g. reproduction. Thus, they influence the sexual differentiation of the genitalia and their functional state in adulthood, the development of secondary sexual characteristics, and sexual behavior. Unlike the lower mammals in which the ovaries and testes are the exclusive source of androgens and estrogens, in humans the adrenals cortex secretes large amount of inactive steroid precursors. These adrenal steroid precursors exert their functions in target tissues after conversion into active estrogens and/or androgens. This phenomenon which describes the conversion and action of steroid hormones within peripheral target tissues has

The rate of formation of each sex steroid hormone depends on the level of expression of the specific enzymes that synthesize androgens and estrogens in each cell of each tissue (Labrie

The final step in the biosynthesis of active steroid hormones is catalyzed by members of the family of 17hydroxysteroid dehydrogenase (17HSD), which comprises different

The 17-hydroxysteroid dehydrogenases (17-HSDs) belong to the short-chain dehydrogenase reductase (SDR) protein superfamily, which also includes the 3 hydroxysteroid dehydrogenase (3HSD). These enzymes regulate the levels of bioactive steroid hormones in many tissues and they are expressed not only in genital tissues, which are the primary target, but also in peripheral blood. The 17-HSDs, along with other steroid

**1.Introduction** 

been called "intracrinology" (Labrie, 1991, 2000).

**2. 17hydroxysteroid dehydrogenases** 

et al., 1998; Stewart § Sheppard, 1992).

enzymes involved in steroidogenesis.

