EFFECTS OF CIS-4-HYDROXY-L-PROLINE ON THE ANDROGEN-INDUCED GROWTH OF THE LATERAL PROSTATE OF THE PREPUBERTALLY CASTRATED GUINEA-PIG

The present study examined the effects of cis-4-hydroxy-L-proline (CHP ), a proline analog, on the androgen-induced growth of the lateral pro state of prepubertally castrated guinea pigs. Prepubertal male guinea pigs were castrated at the age of 3 weeks and allowed to recover compl etely 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 CH P and dihydrotestosterone (DHT) (10 mg/kg/day) for IO days. Control an imals were injected with saline and DHT only. At the end of the experi ment, the lateral prostate was removed and examined by I) conventional transmission electron microscopy (TEM), 2) staining of proteoglycans (PGs) by Cuprolinic Blue (CB) using the critical electrolyte concentra tion (CEC) method, 3) carbohydrate and lectin histochemistry, and 4) e lectron 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 co lumnar 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 comp osed of stromal cells separated by large intercellular spaces with ver y sparse collagen fibrils, and a decrease in stromal PGs especially th ose PGs normally associated with collagen fibrils. CHP treatment also caused perturbation and disorganization in the epithelial basement mem brane. The results suggested that stromal collagen is essential in med iating the response of glandular cells to DHT stimulation. Defective s tromal collagens hamper the responsiveness of prostatic gland to andro gen. (C) 1993 Wiley-Liss, Inc.