Neonatal Hypothyroidism Alters the Pattern of Prostatic Growth and Differentiation, as Well as Plasminogen Activator and Metalloprotease Expression, in the Rat1

Abstract

The purpose of this study was to examine whether changes in growth, ductal histology, and expression of plasminogen activator (PA) and matrix metalloproteases are associated with the increased prostatic weight and DNA content seen in adult rats that were treated neonatally with the goitrogen 6-propyl-2-thiouracil (PTU). Ventral prostatic weights were initially reduced in PTU-treated rats but were increased 40% over those of controls by Day 180; this increase in prostatic weight was also accompanied by increases in the number of prostatic ductal tips. In controls, prostatic PA and gelatinase A activities decreased after completion of morphogenesis at 21-28 days of age. In contrast to controls, PA and gelatinase A activities were maintained through puberty (42 days) in PTU-treated rats but declined by 90 days. The elevated PA activity in both prostatic lobes at 42 days of age in PTU-treated rats was inhibited by amiloride, indicating that it is the urokinase form of PA. These data show that the increased prostatic weight and DNA content in adult rats following neonatal PTU treatment results from a delayed but extended period of growth and the formation of new ductal elements. There is a temporal overexpression of urokinase and gelatinase A associated with the increased ductal branching, indicating as well an extended period of morphogenesis that results in their eventual increased adult size. The prostatic enlargement in PTU-treated rats may serve as a useful model to study regulation of both normal and abnormal prostatic growth and morphogenesis.