hAolecular and ca Ilular iindochohqy Molecular and Cellular Endocrinology 119 (1996) 123-127 Effect of testosterone on purine metabolism and morphometric parameters in the rat liver L. Vizzotto”, M. Vartemati”, E. Marinellob-*, R. Leoncinib, R. Paganib, M. Pizzichinib zyxwvutsrqponmlk “Istituto di Anatomia Umana Normale. Universitd di Milano, Milan, Ita1.v bIstituto di Biochimica e di En:imologia, Universitir di Siena. Pian dei Mantelhi, 44, 53100 Siena, Italy Received 31 July 1995; revised 28 February 1996; accepted 28 February 1996 Abstract The effect of testosterone on the morphology and biochemistry of adult castrated rat liver is described. Castration decreases mean weight and volume of hepatocytes, volume and surface area of sinusoidal lumen, and apparently increases cell number per g of tissue. These variations indicate cell distress. Testosterone administration restored sinusoidal volume and surface area, indicating a true hyperplastic response and improved trophic conditions. Acid soluble nucleotides, RNA and DNA content were lower after castration, being partially restored after testosterone treatment. This restoration, however, was only statistically significant for total guanylate. We concluded that testosterone deficiency and administration exerts a specific effect on the liver in terms of morphological and biochemical changes. Purine nucleotide metabolism is probably the first target of hormonal action, since its changes are the most significant and useful to explain all the other observations. Keywords: Testosterone; Rat liver; Morphometrics; Purine metabolism; Castration zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONML 1. Introduction The influence of hormone on target organs can be understood only when studied through different meth- ods. The morphological and biochemical effects of testosterone have been extensively observed in sexual organs, such as perineal muscle (LAM) [1,2]. Much less research has been carried out on organs not considered to be specific targets, for instance the liver. It is known that liver contains testosterone receptors [3,4]. The only effects reported are described in terms of slight ‘atro- phy’ [5,6], in the framework of a general atrophy which is evident in a castrated animal, as demonstrated by a slight loss of body weight. Abbreviations: ADP, adenosine diphosphate: AMP, adenosine 5’- monophosphate; ATP, adenosine triphosphate; C, castrated rats: GDP, guanosine diphosphate: GMP, guanosine 5’-monophosphate; GTP, guanosine triphosphate; IMP, inosine 5’-monophosphate: IDP. inosine diphosphate; ITP, inosine triphosphate; N, normai rats (sham operated); T, testosterone-treated rats; PCA, perchloric acid. * Corresponding author, Istituto di Biochimica e di Enzimologia, Universita di Siena, Pian dei Mantellini, 44, 53100 Siena, Italy. Tel.: + 39 577 298026. Fax: + 39 577 298057. We decided to study the morphological and biochem- ical effects of testosterone on liver, in normal and castrated rats, before and after administration of testos- terone. The morphological study invoived the evalua- tion of the following parameters: volume and size distribution of hepatocytes and of their nuclei, sinu- soidal bed volume and surface area, and extraparenchy- ma1 volume. The biochemical study consisted in the evaluation of purine nucleotide metabolism. Purine nu- cleotides are represented in the liver (and in all tissues) at different degrees of phosphorylation: AMP, ADP, ATP, GMP, GDP, GTP, IMP, IDP, ITP. Their physio- 2 zyxwvutsrqpo RNA &cursors zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPON (PaPP. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA (de nova synthatr) ’ fomme) Nuc’wides .-7zzzG+\ DNA 1 c.abohsm uric a c id . a llm to in Scheme I. 0303-7207/96/$15.00 0 1996 Elsevier Science Ireland Ltd. All rights reserved PII SO303-7207(96)03797-5