Sex-Related Differences in Plasminogen Activator Activity and Plasminogen Activator Inhibition of Human and Animal Kidneys: Effect of Orchidectomy or Ovariectomy

Abstract

Plasminogen activator activity (PAA), plasminogen activator inhibition (PAI) and plasmin inhibition (PI) have been studied with spectrophotometric methods in extracts of human, bovine, ovine and rat kidneys of both sexes. In all species studied, renal PAA (cortex or medulla) was higher in females than in males. The PAA was also higher in the medulla than in the cortex in all species and both sexes. The PAA was due to both types of plasminogen activator; tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). In the human kidney (cortex or medulla) the measurement of t-PA antigen showed that t-PA is higher in females than in males; t-PA is also higher in the medulla than in the cortex in both sexes. The PAI showed the opposite pattern in all species studied; it was lower in females than in males. It was also lower in the medulla than in the cortex. PAI-1 was identified in the human kidney. Sex-related differences in renal PAA or PAI almost disappeared after bilateral orchidectomy in rats. PI showed no sex or regional differences in the species studied. Sex-related differences in renal PAA and PAI in man and various animal species might be of physiological or pathophysiological importance.

The fibrinolytic system attenuates vascular tone: effects of tissue plasminogen activator (tPA) and aminocaproic acid on renal microcirculation

“…We have speculated that an intact thrombolytic system may be especially important within the outer medulla, since hypoxia‐induced shift of the anticoagulant/procoagulant balance to favor activation of coagulation ( Gertler et al , 1993 ; Pinsky et al , 1998 ) may predispose to a further compromise of medullary oxygenation. The observation that the renal medulla is the principal source of renal PAs ( Smokovitis et al , 1991 ) further supports this hypothesis.…”

“…Furthermore, the unique structure and low flow within the medullary microcirculation (Jamison & Kriz, 1982) may also promote coagulation. The importance of an efficient anticoagulant activity in the outer medulla is emphasized by the the predominant medullary expression of the fibrinolytic system ( Smokovitis et al , 1991 ). There is a prominent expression of tPA mRNA within the renal venular endothelium, and tubular uPA antigen is abundantly found in the deep cortex and outer medulla ( Xu et al , 1996 ).…”

Comparative Studies of Ovarian Steroids in Blood, and Specific Proteolytic Enzymes in the Cervical Mucus, in Four Sheep Breeds after Oestrus Synchronization (Progesterone and PMSG). 2. Breed Variation of PAA, PAI and PI in the Cervical Mucus during Natural Oestrus, Synchronized Oestrus, and the First Oestrus after Synchronized Oestrus

“…PAS and plasmin activity are controlled by plasminogen-activator inhibitors (PAIs) and plasmin inhibitors (PIS), respectively, that occur in body fluids and tissues. Plasminogen activation, besides dissolving blood clots (fibrinolysis), has also been implicated in several other physiological or pathophysiological processes requiring extracellular proteolysis, which include ovulation, embryo implantation, mammary-gland involution, cell migration, epithelial differentiation, neovascularization, and tumour invasion (Dan@ et al 1985;Smokovitis et al 1987Smokovitis et al ,1988Smokovitis et al , 1989Smokovitis et al , 1992a.…”