Neonatal programming of androgen responsiveness of liver of adult rats

J. A. Gustafsson, A. Stenberg

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71 Scopus citations

Abstract

The effects of testosterone propionate treatment of adult male rats castrated at birth and 14 days after birth were studied with respect to the metabolism of 5α [4 14C] androstane 3α,17β diol and 4 [4 14C] androstene 3,17 dione in the liver microsomal fraction and the metabolism of 4-[4-14C] androstene 3, 17 dione in the 105,000 x g supernatant fraction of liver. Microsomal 2β and 7β hydroxylation of 5α androstane 3α,17β diol was only measurable after testosterone treatment of rats testectomized at 14 days of age. Likewise, 18 hydroxylation of 5α androstane 3α, 17β diol and 6β hydroxylation of 4 androstene 3,17 dione increased 2.9 and 2.6 times, respectively, after testosterone treatment of rats castrated 14 days after birth, whereas these hydroxylations only increased 1.2 and 1.3 times, respectively, after testosterone treatment of rats castrated at birth. On the other hand, testosterone treatment increased the activity of the 5β reductase (in the cytosol fraction) 3.9 times in neonatally castrated rats but decreased the activity of the enzyme by about 20% in rats castrated 14 days after birth. These results indicate that testicular secretion products, probably androgen(s), imprint the liver during the postnatal period so that it responds differently to androgens in adult life than if neonatal androgenic influence does not occur. The changed androgen responsiveness of liver could be related to changed androgen metabolism; changed concentrations of cytoplasmic or nuclear receptor proteins, or both; and changed expression of genetic information.

Original languageEnglish (US)
Pages (from-to)719-723
Number of pages5
JournalJournal of Biological Chemistry
Volume249
Issue number3
StatePublished - 1974

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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