Oestrogen receptor deficiency: consequences for growth.
These oestrogen-resistant and aromatase-deficient cases now establish a more complete picture of how androgen and oestrogen combine to regulate pubertal growth (47, 48) and demonstrate that oestrogen deficiency states need not be lethal (1). Whereas original concepts suggested that skeletal maturation and pubertal growth were attributable to androgen and, therefore, were not sexually dimorphic, current evidence preserves the notion of common mechanisms in both sexes, but points to oestrogen as the principal steroid involved in the final phases of skeletal maturation. Oestrogen can be viewed as a primary determinant of the final height of a child, in the sense that oestrogen initiates and completes epiphyseal closure. The full scope of the effects of androgen on epiphyseal maturation and linear height regulation is less clear but evidence suggests that androgen has direct and indirect effects through its aromatization to oestrogen (Fig. 2). Remarkably, under unusual circumstances, a rather prolonged period of continued growth can be achieved with minimal bone-age advancement, as long as oestrogen concentrations and/or sensitivity are low. Given this more complete understanding of the role of oestrogen, and with the availability of more sensitive assays for oestradiol (49), a new era in sex-steroid physiology and pubertal growth has been inaugurated (50). However, any therapies directed towards manipulating growth with sex steroids will need to take account of the possibility of untoward effects on other processes, such as the accretion of bone mineral mass (51,52).
Smith
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Children's Hospital Medical Centre, Cincinnati, Ohio, USA.
Korach
K S
KS
D000293:Adolescent; D000728:Androgens / Q000502:physiology; D001141:Aromatase / Q000172:deficiency; D002113:Calcification, Physiologic / Q000502:physiology; D004967:Estrogens / Q000502:physiology; D005260:Female; D006128:Growth / Q000502:physiology*; D006801:Humans; D008297:Male; D011960:Receptors, Estrogen / Q000172:deficiency*
D000728:Androgens; D004967:Estrogens; D011960:Receptors, Estrogen; D001141:Aromatase