The effects of estrogens on linear bone growth

Regulation of linear bone growth in children and adolescents comprises a co mplex interaction of hormones and growth factors. Growth hormone (GH) is co nsidered to be the key hormone regulator of linear growth in childhood. The pubertal increase in growth velocity associated with GH has traditionally been attributed to testicular androgen secretion in boys, and to oestrogens or adrenal androgen secretion in girls. Research data indicating that oest rogen may be the principal hormone stimulating the pubertal growth spurt in boys as well as girls is reviewed. Such an action is mediated by oestrogen receptors (ER-alpha and ER-beta) in the human growth plate, and polymorphi sms; in the ER gene may influence adult height in healthy subjects. Prepube rtal oestradiol concentrations are significantly higher in girls than in bo ys, explaining sex-related differences in pubertal onset. Men with a disrup tive mutation in the ER gene (oestrogen resistance) or in the CYP19 gene (a romatase deficiency) who have no pubertal growth spurt and continue to grow into adulthood due to lack of epiphyseal fusion supports this notion. Furt hermore, phenotypic females with complete androgen insensitivity syndrome h ave a normal female growth spurt despite lack of androgen action. Oestrogen s may also influence linear bone growth indirectly via modulation of the GH -insulin-like growth factor-I (IGF-I) axis. Thus, ER blockade diminishes en dogenous GH secretion, androgen receptor (AR) blockade increases GH secreti on in peripubertal boys, and non-aromatizable androgens [oxandrolone or dih ydrotestosterone (DHT)] have no effect on GH secretion. Treatment with arom atase inhibitors reduces circulating IGF-I concentrations in healthy males, and reduces growth in boys with testotoxicosis. Taken together, these find ings suggest that oestrogens may, in addition to their direct effects, stim ulate GH secretion and thereby increase circulating IGF-I, which in turn ma y stimulate growth. Thus, oestrogens have important biphasic actions on lon gitudinal growth in boys as well as in girls. Very low levels of oestrogens may stimulate bone growth without affecting sexual maturation directly at the growth plate as well as through stimulation of the GH-IGF axis, which i n turn may stimulate growth. Conversely, higher levels of oestrogens stimul ate secondary sexual characteristics and epiphyseal fusion.