ABSTRACT
Androgens accelerate bone maturation, but it is unclear to what extent this process may be mediated by estrogens derived from aromatization of androgens. In this study, we investigated whether an estrogen-blocking agent, Faslodex (ICI 182,780), can attenuate testosterone-accelerated skeletal maturation in immature mice. On days of life 2-8, mouse pups received either testosterone propionate (50 microg/100 g body weight), Faslodex (100 microg/100 g body weight), a combination of Faslodex + testosterone, or vehicle alone. Skeletal maturation was assessed in the forepaw and the lumbar spine. Testosterone caused acceleration of bone maturation (p < 0.05, compared with vehicle), predominantly of axial bones. Faslodex, however, failed to block the effect of testosterone, such that the mice receiving Faslodex + testosterone had skeletal maturation scores similar to those treated with testosterone alone. These results suggest that androgens have the capacity to stimulate bone maturation directly, probably via their own receptors.
Subject(s)
Bone Development/drug effects , Estradiol/analogs & derivatives , Estradiol/pharmacology , Estrogen Antagonists/pharmacology , Testosterone/pharmacology , Animals , Drug Interactions , Fulvestrant , Mice , Mice, Inbred C57BLABSTRACT
Sex steroids accelerate bone maturation, but it is believed that estrogen action is needed for terminal epiphyseal fusion. In this study, we investigated the effects of a new estrogen-blocking agent, Faslodex (ICI 182,780), on estrogen-accelerated skeletal maturation in immature mice. On day-of-life 2 through 8, mice pups received either estradiol (5 microg/100 g body weight), Faslodex (100 microg/100 g body weight), a combination of Faslodex + estradiol, or vehicle alone. Skeletal maturation was assessed with a scoring system based on the size and appearance of epiphyseal plates in the forepaw and the lumbar spine. Estradiol caused acceleration of bone maturation in our mouse model (p < 0.05). Faslodex blocked the effect of estrogen, such that the mice receiving Faslodex + estradiol did not vary significantly from controls. Faslodex may prove useful in the treatment of patients with diseases causing rapid skeletal maturation, such as precocious puberty.
Subject(s)
Bone Development/physiology , Estradiol/analogs & derivatives , Estrogen Antagonists/pharmacology , Estrogens/physiology , Receptors, Estrogen/physiology , Animals , Animals, Newborn , Bone Development/drug effects , Estradiol/pharmacology , Fulvestrant , Mice , Receptors, Estrogen/antagonists & inhibitorsABSTRACT
Long term follow-up studies of children with congenital adrenal hyperplasia have documented less than desirable outcomes, including reduction in final adult height, obesity, virilism, and decreased fertility. We have proposed that children with the most severe forms of congenital adrenal hyperplasia would be better off if their adrenals were removed at an early age. We report here on our experience with prophylactic bilateral adrenalectomy in a 3-yr-old girl with a double null mutation of the CYP21 gene. The results of sodium balance studies, performed preoperatively on our patient and her unaffected fraternal twin sister, and hormonal data are presented as well. In contrast to her twin, who markedly increased her sodium retention in response to ACTH, our patient showed increased natriuresis, suggesting a deleterious effect of her adrenals on sodium homeostasis. Adrenalectomy was carried out at the time of necessary genital repair. No surgical or postsurgical complications were encountered.
