Androgens in Health and Disease.pdf - E Library

Chapter 5/Estrogen Action in Males 89
5 Estrogen Action in Males
Insights Through Mutations in Aromatase
and Estrogen-Receptor Genes
Jonathan Lindzey, PhD
and Kenneth S. Korach, PhD
CONTENTS
INTRODUCTION
BEHAVIOR
HORMONES
TESTIS AND DUCTULE STRUCTURES
ACCESSORY SEX STRUCTURES
CLINICAL PRESENTATIONS
CONCLUSIONS
REFERENCES
INTRODUCTION
Testosterone (T) exerts a wide range of effects that span many life stages and are
absolutely critical for successful reproduction in male vertebrates. For instance, T
secreted by the embryonic and/or neonatal testes plays a critical role in sexual differentiation
of internal and external genitalia (1), accessory sex structures (2), and organization
of the central nervous system (CNS) (3). Pubertal increases in T play critical roles
in pubertal maturation (4) and T continues to play critical roles in activation of sex
behaviors (5), regulation of the hypothalamic–pituitary–gonadal axis (6) and stimulation
of peripheral reproductive structures in adult males (2). In addition, it has become
more widely accepted that T also plays critical roles in nonreproductive effects such as
bone growth and expression of renal and hepatic enzymes.
At the cellular level, these diverse actions of T can be mediated by several different
paths (see Fig. 1): (1) interaction of T with androgen receptors (ARs), (2) conversion of
T into 5α-dihydrotestosterone (5α-DHT) by 5α-reductase and subsequent interactions
with AR, or (3) conversion of T into 17β-estradiol (E 2) by P450aromatase (CYP19) and
subsequent interactions with estrogen receptors (ERs) (the “aromatization hypothesis”).
For instance, direct activation of AR by T is required for normal development of wolffian
derivatives such as the seminal vesicle, whereas conversion to 5α-DHT is required for
From: Contemporary Endocrinology: Androgens in Health and Disease
Edited by: C. Bagatell and W. J. Bremner © Humana Press Inc., Totowa, NJ
89