Effects of cis‐4‐hydroxy‐L‐proline on the androgen‐lnduced growth of the prostate of the prepubertally castrated guinea pig

Abstract

The present study examined the effects of cis-4-hydroxy-L-proline (CHP), a proline analog, on the androgen-induced growth of the lateral prostate of prepubertally castrated guinea pigs. Prepubertal male guinea pigs were castrated at the age of 3 weeks and allowed to recover completely before subjection to an experimental regime to alter the stromal collagen synthesis by CHP. The animals were kept on a special proline-deficient diet (PDD) for a week before the subcutaneous injection of CHP (200 mg/kg/day) for 3 days, followed by a combined injection of CHP and dihydrotestosterone (DHT) (10 mg/kg/day) for 10 days. Control animals were injected with saline and DHT only. At the end of the experiment, the lateral prostate was removed and examined by 1) conventional transmission electron microscopy (TEM), 2) staining of proteoglycans (PGs) by Cuprolinic Blue (CB) using the critical electrolyte concentration (CEC) method, 3) carbohydrate and lectin histochemistry, and 4) electron microscopy (EM) lectin-gold labelling. The results showed that the wet weight of prostate from CHP-treated animals was significantly lower than the control and recovery groups. The epithelium was low columnar with an obvious increase in intercellular spaces and number of basal cells. The glandular cells showed little secretory activity with a decrease in number of granular endoplasmic reticulum (GER) profiles, secretory granules, and a small Golgi apparatus. The stroma was composed of stromal cells separated by large intercellular spaces with very sparse collagen fibrils, and a decrease in stromal PGs especially those PGs normally associated with collagen fibrils. CHP treatment also caused perturbation and disorganization in the epithelial basement membrane. The results suggested that stromal collagen is essential in mediating the response of glandular cells to DHT stimulation. Defective stromal collagens hamper the responsiveness of prostatic gland to androgen.

Altered expression of extracellular matrix and proteinases in noble rat prostate gland after long‐term treatment with sex steroids

“…Early studies in castrated and pubertal rat prostates have demonstrated the importance of collagens in the growth regulation of prostate gland [9±12]. Its importance is further demonstrated by the studies of metabolic inhibition of collagen synthesis in the androgen-stimulated castrated prostates, and such inhibition can effectively prevent the growth of prostate [11,13,14], suggesting that the androgenstimulated growth of prostate is mediated by the stromal collagens. Tenascin, an extracellular matrix glycoprotein, is believed to play a role in epithelialstromal interactions in some hormone-dependent organs including prostate.…”