Actions of Androgens on the Kidney of Female Mice: Strain Differences in the DNA and β‐Glucuronidase Responses

Abstract

The anabolic effects of testosterone on kidneys from two strains of female mice were studied over a course of 25 days. The A/J and C57BL/6J strains were selected because they carry regulatory alleles Gura and Gurb which determine rapid and slow induction of β‐glucuronidase, respectively. (A major goal of this study was to determine whether these mouse strains have other differences in their responses to testosterone). The wet weight, dry weight and total protein content of the kidneys of both strains increased about 70% in both strains. Total RNA increased 112% and 93% in a biphasic manner in the A/J and C57BL/6J mouse strains, respectively. The steep slope during the first 5 to 7 days was attributed to a selective stimulation of RNA accumulation while the latter, less rapid, RNA increase occurred in parallel with tissue growth. The total DNA content of kidneys from testosterone treated A/J mice never increased above that of controls, indicating that hypertrophy could account for renal enlargement in this strain. By contrast, testosterone treatment produced a 24% increase in total kidney DNA in C57BL/6J mice, signifying that both hypertrophy and hyperplasia are important factors in the anabolic response of this strain. These observations indicated another difference in the androgen induced response of A/J and C57BL/6J mice. As a consequence of the testosterone stimulated increase in renal β‐glucu‐ronidase synthesis, the excretion of the lysosomal form of the enzyme into the urine increased 2200‐fold in A/J but only 57‐fold in C57BLIGJ. The total enzyme activity excretedidayimouse was only 4 times higher in A/J versus C57BLi6J with the differences reflecting the basal activity which was 10‐fold higher in C57BLIGJ mice. The basal excretion of another lysosomal enzyme, β‐galactosidase, was also several fold higher in C57BL/6J, suggesting that lysosomes in those animals are either larger or their contents are excreted at a faster rate.

Effect of Castration and Testosterone Substitution on the Urinary Output of Gamma-Glutamyl Transpeptidase and of N-Acetyl-Beta-D-GIucosaminidase of Male Rats with Renovascular Hypertension

“…Independently from the observed range, however, it is characteristic for all three groups that animals with higher blood pres sures had a higher daily yGT excretion rate than those with a less expressed hypertension ( fig-O-As shown in table I testosterone affected not only the output of yGT, but also that of NAG: with ~ 8 U/g creatinine castrates ex creted the same amount as untreated female rats [see 17], i.e., far less than hypertensive males or hypertensive, testosterone-substi tuted castrates. This finding is in good accor dance with the results of Koenig et al [8] and Mills et al [20] who showed that in the absence of testosterone the secretion rate of lysosomal hydrolases is generally reduced. Furthermore, there is one special circum stance of the NAG output which deserves consideration: the existence of a positive cor relation between the NAG output and the HP content of the kidneys of hypertensive male rats and testosterone-substituted castrates ( fig.…”

“…Sex differences in the enzyme architecture of the rat kidney have been known for a long time [1], Especially the effect of the male sex ual hormone on the histology of the kidney and on the activity of certain enzymes has been extensively studied [7,8,20,22,23,25]. Thus, it was shown that the administration of testosterone causes renal hypertrophy and in creases the protein content of the kidney [2,6,9,24], However, nothing is known about the cause of sex differences in the urinary output of enzymes, e.g., yGT.…”

Sex-related differences in renal size in mice: ontogeny and influence of neonatal androgens

“…This renal enlargement was secondary to both cellular hyperplasia and hypertrophy, since in males there was a greater increase in cell number and protein concentration. In agreement with the findings of Kochakian (1975), Bardin et al (1978 ) and Mills et al (1979), the present results show that the increase in kidney weight in adult females treated with testosterone was secondary to cellular hypertrophy rather than hyperplasia. The kidney weight of these testosterone-treated adult female mice remained smaller than that of males and this difference could be attributed to the reduced basal number ofcells which was not increased by androgen treatment.…”

“…In mice, but not in all species, renal size is reduced by orchidectomy, while administration of testosterone stimulates a marked response of the kidney as indicated by an increase in the synthesis of nucleic acids and protein (Selye, 1939;Kochakian, 1959Kochakian, , 1975Mills, Mills, Yurkiewicz & Bardin, 1979). The sex-related difference in kidney size has been attributed to the androgenic status of the animal, and the mouse kidney has become an important tissue for studying the mechanism of androgen action (Bardin, Bullock, Sherins et al 1973;Bardin, Brown, Mills et al 1978 ).…”

Androgen induction of ornithine decarboxylase mRNA in mouse kidney as studied by complementary DNA.

“…Testosterone administration markedly increases the activity of OrnDCase and other proteins in mouse kidney (5,6,14,15,(33)(34)(35) and produces cellular hypertrophy rather than hyperplasia (35). The induction requires functional androgen receptors and is seen as early as a few hours after hormone administration (5,34).…”