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The NADP-dependent microsomal kidney enzymes, 3- and 20β-hydroxysteroid dehydrogenase (HSDH), which exhibit considerable sex differences in their activities (male: female activity ratios, 16:1 and 30:1 respectively), were investigated after interference with the pituitary–gonad and pituitary–adrenal systems.

Prepubertal gonadectomy as well as hypophysectomy of mature male rats led to a decline in HSDH activity to almost that found in the normal female rat, whereas activities in female rats were unaffected. Testosterone induced typical male 3-HSDH activity in both gonadectomized and hypophysectomized rats of either sex. Administration of 5-dihydrotestosterone (5-DHT) or 5-androstane-3, 17β-diol to hypophysectomized male rats was equally effective in restoring full 3- and 20β-HSDH activities whereas 5-androstane-3β, 17β-diol was less effective and dehydroepiandrosterone was ineffective. Simultaneous administration of cyproterone acetate did not block the inductive action of 5-DHT.

Administration of chorionic gonadotrophin, pregnant mare serum gonadotrophin or a combination of luteinizing hormone and follicle-stimulating hormone to hypophysectomized male rats all led to parallel increases in the weight of the seminal vesicles and in both renal enzyme activities; administration of growth hormone, prolactin or thyroid-stimulating hormone was ineffective.

Adrenalectomy of gonadectomized, but not of hypophysectomized male rats, caused a further drop in activity to the normal female level. Adrenalectomy of otherwise intact rats did not affect either enzyme activity.

The hypophysis was involved in the regulation of the two NADP-dependent renal HSDH activities through its gonadotrophic function in male rats; adrenal secretions were of little physiological significance.