390 CELLS, TISSUES, AND ORGANISMS 



gens to children with stunted growth will also accelerate skeletal mat- 

 uration, which will become evident on X-ray during the treatment 

 period of three months or six to twelve months after treatment. High 

 doses of methyl testosterone, of the order of 30 mg. or more a day, 

 may increase the rate of epiphyseal changes. 



Linear growth: estrogenic steroids 



Sources of estrogens. Estrogens are produced in large amounts by 

 the ovary and, during pregnancy, by the placenta. Estrogen is also 

 secreted to a lesser degree by the adrenal cortex of both sexes. Es- 

 tradiol, estrone, and estriol are the main estrogens that have been iso- 

 lated from human tissues and body fluids, and both estradiol and 

 estrone have been recovered from the ovaries of the sow. Estrone is 

 present in small quantities in male urine. 



Estrogen production with age. Boys and girls secrete small con- 

 stant amounts of estrogen until about the age of seven. Excretion then 

 increases slightly but remains similar in both sexes to the age of ten or 

 eleven (Nathanson, Towne, and Aub, 1941). At this time estrogen pro- 

 duction in the female shows a dramatic increase, and cyclic changes in 

 excretion begin to occur (Figure 3). The amount of gonadotropic 

 follicle-stimulating hormone (FSH) secreted by the pituitary gland is 

 also increased at this time, as judged by the increased urinary levels. 

 Only minute amounts of FSH are excreted before puberty. Estrogen 

 excretion also increases during this period in the male, but to a much 

 lesser extent, being derived from the adrenal gland. 



The fact that boys and girls secrete equal amounts of estrogen be- 

 fore puberty suggests that in early childhood the hormone is not de- 

 rived from the ovary. There is sufficient evidence to point to the 

 adrenal gland as the source of the estrogen. However, at puberty the 

 ovary becomes active, and estrogen production is markedly increased. 

 The increase in estrogen production does not occur in a castrated indi- 

 vidual or in certain pathological conditions. 



What role estrogens play, if any, in normal preadolescent growth 

 is poorly understood. In cases of ovarian agenesis, there occurs re- 

 tarded growth and osteoporosis. Sexual maturity does not occur; the 

 girls reach a height of only 50 to 58 inches; and there is a moderate 

 delay in epiphyseal fusion ( Wilkins and Fleischmann, 1944 ) . However, 

 the syndrome of ovarian agenesis is often associated with congenital 

 defects, and the short stature also is thought to be a genetic defect. In- 

 terestingly, the 17-ketosteroid excretion is low, indicating the additional 

 factor of adrenal-cortical depression. In the opposite situation a granu- 

 losa cell tumor of the ovary ( which secretes large amounts of estrogen ) 

 causes acceleration of growth and advanced bone development. 



