The effects of oestrogens 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. prepuber tal oestradiol concentrations are significantly higher in girls than in boy s, explaining sex-related differences in pubertal onset. Men with a disrupt ive mutation in the ER gene (oestrogen resistance) or in the CYP19 gene (ar omatase deficiency) who have no pubertal growth spurt and continue to grow into adulthood due to lack of epiphyseal fusion supports this notion. Furth ermore, phenotypic females with complete androgen insensitivity syndrome ha ve a normal female growth spurt despite lack of androgen action. Oestrogens may also influence linear bone growth indirectly via modulation of the GH- insulin-like growth factor-I (IGF-I) axis. Thus, ER blockade diminishes end ogenous GH secretion, androgen receptor (AR) blockade increases GH secretio n in peripubertal boys, and non-aromatizable androgens [oxandrolone or dihy drotestosterone (DHT)] have no effect on GH secretion. Treatment with aroma tase inhibitors reduces circulating IGF-I concentrations in healthy males, and reduces growth in boys with testotoxicosis. Taken together, these findi ngs suggest that oestrogens may, in addition to their direct effects, stimu late GH secretion and thereby increase circulating IGF-I, which in turn may stimulate growth. Thus, oestrogens have important biphasic actions on long itudinal growth in boys as well as in girls. Very low levels of oestrogens may stimulate bone growth without affecting sexual maturation directly at t he growth plate as well as through stimulation of the GH-IGF axis, which in turn may stimulate growth. Conversely, higher levels of oestrogens stimula te secondary sexual characteristics and epiphyseal fusion.