The ontogeny of uterine pathology and pathophysiology following neonatal androgen administration.

Abstract

These experiments show altered uterine cell functions following neonatal androgen treatment in the Holtzman subline of Sprague-Dawley rats. Litter size was limited to 8. Females which were androgenzied (AF) received a single sc dose of 1.25 mg testosterone propionate on Postnatal Day 3 or 4. Control females (NF) received only the sesame oil twice daily. Other females received 2 mcg of EB or vehicle twice daily. Estrogeninduce protein was found to be the same in propubettal normal and AF females. With 1 exception uterine weights were similar in NF controls and AF animals at all ages. Ovariectomy on Day 23 caused similar atrophy estrogen administration given on Day 23 there was a marked difference in the response of NF and AF animals. In weanlings the specific activity of trichloracetic acid (TCA) precipitable proteins was similar in control and in estrogen-stimulated NF and AF animals. At 38 days tissue glycogen levels were higher in NF than in AF animals but at 66 days of age glycogen in NF animals was only 1/3 of that in AF animals. Histological differences in the uteri were 1st detectable at 20 days of age and were progressive. Ovarian tissues showed no differences. At 2 months of age AF animals showed squamous metaplasia of the endometrial lining. At 3 months of age this was more extensive and muscle thickness was increased. The action of testosterone was apparently directly at the level of uterus. The presence of an ovary was needed for the complete expression of the syndrome of androgenization. Data suggest that in the female rat early androgen therapy alters the metabolism of steroid responsive cells and that ovarian hormones are related to the expression of altered uterine function.