ABSTRACT
BACKGROUND: Oxytocin (OT) is one of the important paracrine factors that prostate synthesizes. OT maintains its resting tone and stimulates its contractile activity. However, the involvement of OT in modulating cell proliferation of the prostate is being investigated. In fact, alterations in OT concentrations accompany both benign prostatic hyperplasia/hypertrophy and carcinoma of the prostate. The enzyme Insulin-regulated aminopeptidase (IRAP) is the main responsible of OT levels regulation through its catabolism. To date, the long-acting selective α(1)-adrenergic receptor antagonist doxazosin is widely used to the treatment of BPH. Thus, our aim was to analyze the effects of doxazosin on IRAP specific activity and its putative effects on prostate OT regulation and functions. METHODS: Fifteen male Wistar rats were treated subcutaneously with 10 mg/Kg doxazosin during 15 days and fifteen controls were treated with the vehicle only. After the treatment period, prostate was removed to obtain soluble and membrane-bound fractions. Soluble and membrane-bound IRAP specific activities were assayed fluorometrically using leucyl-ß-naphthylamide as substrate. Prostate OT content was assayed by enzyme immunoassay. RESULTS: Doxazosin treatment significantly increased membrane-bound IRAP specific activity in rat prostate by 59.4%, whereas no changes were observed in the soluble fraction. Treatment with doxazosin also significantly increased OT concentration by 26.3%. CONCLUSIONS: In vivo administration of doxazosin to male rats modify both prostatic IRAP activity and OT levels. Because there is now evidence that OT plays a physiological role in the regulation of growth and muscular contractility within the gland, more attention should be paid to IRAP activity, which could represent a new target for the regulation of the functions of OT under physiological or pathological conditions such as BPH and prostate cancer.
Subject(s)
Adrenergic alpha-1 Receptor Antagonists/pharmacology , Cystinyl Aminopeptidase/drug effects , Doxazosin/pharmacology , Prostate/drug effects , Animals , Cystinyl Aminopeptidase/metabolism , Immunoenzyme Techniques , Male , Muscle Contraction/drug effects , Oxytocin/drug effects , Oxytocin/metabolism , Prostate/metabolism , Rats , Rats, Wistar , Receptors, Adrenergic, alpha-1/drug effects , Receptors, Adrenergic, alpha-1/metabolismABSTRACT
The hypothalamus-pituitary-adrenal axis (HPA) participates in the maintenance of cardiovascular functions and in the control of blood pressure. By other hand, it is known that blood pressure regulation and HPA activity are affected by sex hormones. The aim of the present work is to analyze the influence of estradiol and progesterone on renin-angiotensin system (RAS)-regulating aminopeptidase A, aminopeptidase B and aminopeptidase N activities and vasopressin-degrading activity in the HPA axis of ovariectomized mice and ovariectomized mice treated subscutaneously with different doses of estradiol and progesterone. Our data suggest that in female mice, estradiol and progesterone influence RAS-regulating and vasopressin-degrading activities at different levels of the HPA axis.
Subject(s)
Aminopeptidases/metabolism , Hypothalamus/metabolism , Pituitary-Adrenal System/metabolism , Renin-Angiotensin System , Vasopressins/metabolism , Animals , Female , Mice , Mice, Inbred BALB C , Solubility , Substrate SpecificityABSTRACT
BACKGROUND: In previous reports, changes in oxytocinase activity in human breast cancer tissue and in the serum of N-methyl-nitrosourea (NMU)-induced rat mammary tumors were described. Insulin-regulated aminopeptidase (IRAP) has been identified with oxytocinase and has also been referred to as placental leucine aminopeptidase (P-LAP). MATERIALS AND METHODS: The IRAP/P-LAP activity in rat serum was assayed to analyze the putative role that IRAP/P-LAP may play in regulating mammary gland carcinogenesis induced by NMU. Furthermore, as it has been recently described that IRAP/P-LAP is the angiotensin IV (Ang IV) receptor AT4, the activities of Ang IV-forming aminopeptidase N (APN) and aminopeptidase B (APB) were also assayed. RESULTS: Changes in serum IRAP/P-LAP and Ang IV-forming APB activities were found in rats with mammary tumors induced by NMU. Both activities were greatly increased, although the Ang IV-forming APN activity was not modified. CONCLUSION: These changes in aminopeptidase activities may reflect the local functional status of their substrates, which can be selectively activated or inhibited in the affected tissue as a result of specific conditions brought about by the tumor. Thus, these enzymatic activities may be involved in the promotion and progression of breast cancer through oxytocin (OT), vasopressin (AVP) and/or renin-angiotensin system (RAS) misregulation.
