Histological and functional changes of the testis tissue during GnRH agonist treatment of prostatic cancer.
The purpose of this study was to examine long-term effects of GnRH agonists on human testicular histology and endocrine function. Patients with advanced prostate cancer (n = 7) were treated with the potent GnRH agonist analogue buserelin (Bu, Hoechst), 600 micrograms X 3/day intranasally. After 6 months, the patients were orchiectomized, and the testis tissue was used for histological studies and measurements of endocrine function in vitro. Fourteen other patients with matching ages and extent of the disease were castrated as the first form of therapy, and their testis tissue was used as controls (C). Severe atrophy of seminiferous tubules was seen in light microscopy in the testes of the Bu treated patients. Many tubules showed only Sertoli cells, and the seminiferous epithelium was frequently absent. In contrast, no clear changes were seen in the number of Leydig cells. Testicular content of testosterone (T) decreased greater than 95% by Bu treatment: C = 1.5 +/- 0.2 nmol/g wet wt (x +/- SE); Bu = 0.070 +/- 0.019 nmol/g. Likewise, a drop of 80% occurred in testicular high affinity receptors for FSH: C = 0.37 +/- 0.019 pmol/g; Bu = 0.067 +/- 0.009 pmol/g. In contrast, the number of LH receptors was unaffected by the treatment, C = 0.18 +/- 0.033; Bu = 0.18 +/- 0.032 pmol/g. When testis slices were incubated in the presence of maximally stimulating concentration of hCG (100 ng/ml), both groups of tissue responded similarly with a 50% increase in T production, albeit the absolute production rate was reduced by 95% in the Bu group. When several steroid precursors of T were analyzed in the incubation media, it appeared that decreased androgen synthesis was most clearly due to decreased 3 beta-hydroxysteroid dehydrogenase activity. It is concluded that long-term treatment with GnRH agonists in prostatic cancer patients brings about dramatic damage of seminiferous tubular function and reduces testicular androgen producing capacity, but has no effect on testicular capability of responding immediately to LH stimulation.
Huhtaniemi
I
I
Department of Physiology, University of Turku, Finland.
Nikula
H
H
Parvinen
M
M
Rannikko
S
S
D000368:Aged; D002064:Buserelin / Q000627:therapeutic use; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004341:Drug Evaluation; D006651:Histocytochemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D011962:Receptors, FSH / Q000187:drug effects / Q000378:metabolism; D011974:Receptors, LH / Q000187:drug effects / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000503:physiopathology*; D013739:Testosterone / Q000378:metabolism; D013997:Time Factors
D006063:Chorionic Gonadotropin; D011962:Receptors, FSH; D011974:Receptors, LH; D013739:Testosterone; D000242:Cyclic AMP; D002064:Buserelin