Endocrinology, Vol 99, 1295-1303, Copyright © 1976 by Endocrine Society

ARTICLES

Androgen receptors in the anterior pituitary and central nervous system of the androgen "insensitive" (Tfm) rat: correlation between receptor binding and effects of androgens on gonadotropin secretion

O Naess, E Haug, A Attramadal, A Aakvaag, V Hansson and F French

The cytosol fractions of the anterior pituitary, hypothalamus, preoptic area and brain cortex of androgen "insensitive" (Tfm) rats possess androgen receptors. However, in the Tfm rats the androgen binding per mg protein was only 10-15% of that in the corresponding normal littermates (Nl). The physicochemical properties of the androgen receptors in the anterior pituitary of the Tfm rat were indistinguishable from those of the normal rat. Thus, no distinctive differences were observed with regard to electrophoretic mobility in 3.25% polyacrylamide gels, isoelectric point (pI=5.8), binding affinity (KD=1.5 X 10(-9)M), temperature stability, sulfhydryl dependence and steroid specificity. It is, therefore, likely that the very low androgen binding capacity by the anterior pituitary and the central nervous system is due to an extreme reduction in the receptor number rather than to the presence of abnormal receptors. Since in the Tfm animals the androgen receptor number is reduced by 85-90%, it is to be expected that very high doses of androgens would be required to achieve hormonal effects. In fact, low doses of 5alpha-dihydrotestosterone propionate (50 mug/100 g body weight) given sc daily for 12 days had no effect on serum levels of LH and FSH. However, very high doses (2 mg/100 g body weight) of testosterone propionate and 5alpha- dihydrotestosterone propionate, which maintained circulating androgen levels above 20 ng/ml, significantly reduced serum gonadotropin levels in castrated Tfm rats. In normal littermates both low and high doses of the androgens suppressed gonadotropin secretion to low levels. These findings strongly indicate that androgen receptors are essential to androgen action on the anterior pituitary and central nervous system in the rat. The serum levels of testosterone (7.7+/-0.15 (SE) ng/ml) and 5alpha-dihydrotestosterone (0.37+/-0.06 ng/ml) were significantly higher in intact Tfm rats than in normal littermates (2.6+/-0.03 and less than 0.1 ng/ml, respectively). The failure of the elevated concentrations of serum androgens to reduce the high serum levels of LH and FSH in intact Tfm rats is most likely due to the extreme reduction of the androgen receptor number and the consequent insufficient hypothalamic and/or pituitary response to androgens.

This article has been cited by other articles:

				J. N. Stallone, R. L. Salisbury, and C. T. Fulton Androgen-receptor defect abolishes sex differences in nitric oxide and reactivity to vasopressin in rat aorta J Appl Physiol, December 1, 2001; 91(6): 2602 - 2610. [Abstract] [Full Text] [PDF]

				C. Bardin and J. Catterall Testosterone: a major determinant of extragenital sexual dimorphism Science, March 20, 1981; 211(4488): 1285 - 1294. [Abstract]

				N. MacLusky and F Naftolin Sexual differentiation of the central nervous system Science, March 20, 1981; 211(4488): 1294 - 1302. [Abstract]

				S. Breedlove and A. Arnold Hormone accumulation in a sexually dimorphic motor nucleus of the rat spinal cord Science, October 31, 1980; 210(4469): 564 - 566. [Abstract] [PDF]