Treatment of Prostatic Cancer with a Gonadotropin-Releasing Hormone Agonist Analog: Acute and Long Term Effects on Endocrine Functions of Testis Tissue*

Abstract

Six patients with advanced prostatic cancer were treated with a potent GnRH agonist analog (buserelin, Hoechst; 600 micrograms, intranasally, three times a day) for 6 months. The first 2-6 days of treatment were associated with a 50% elevation (P less than 0.01) in serum testosterone (T) and a simultaneous elevation of 20% (P less than 0.01) in serum prostate-specific acid phosphatase (PAP). Serum T fell to the castrate range (less than 1 nmol/liter) in all patients in 2-3 weeks, and PAP decreased concomitantly in five of the six patients. Serum LH progressively decreased by about 80% during the treatment, whereas a secondary rise of FSH levels occurred after the first month of treatment. The patients were orchiectomized after 6 months of treatment. No differences were found between the pre- and postsurgical levels of serum T or in comparison with those of six patients orchiectomized as the first therapeutic measure. Testicular endogenous T concentrations, LH and FSH receptors, and in vitro T production were measured in three testis samples and compared with those values in testis tissue obtained from five control patients. The endogenous levels and in vitro production of T were depressed by over 95% in testes from agonist-treated patients. The small residual T production responded to hCG stimulation as in control patients. Interestingly, no change was found in testicular LH receptor content, but FSH receptors decreased by 80%. The elevation in serum PAP at the beginning of the agonist treatment and the small residual testicular T production after 6 months may not be clinically important. However, they indicate the necessity of comparative long term studies between orchiectomy and GnRH agonists in the treatment of patients with prostatic cancer.

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

“…The sera were extracted twice with 2 mL diethyl ether and evaporated to dryness. The residues were reconstituted in PBS with 0.1% BSA and measured using standard RIA, as described previously (Huhtaniemi et al ., 1985). The sensitivity of the assay was 1 nmol/L.…”

Loss of Bmyc results in increased apoptosis associated with upregulation of Myc expression in juvenile murine testis

“…Testosterone was measured from diethyl ether extracts using RIA (Huhtaniemi et al 1985), and FSH and LH were measured by immunofluorometric assays as described previously (Haavisto et al 1993, van Casteren et al 2000. Intratesticular testosterone was analyzed by homogenizing one weighed testis in 5 ml PBS from 11 KO and eight WT mice.…”

High levels of luteinizing hormone analog stimulate gonadal and adrenal tumorigenesis in mice transgenic for the mouse inhibin-α-subunit promoter/Simian virus 40 T-antigen fusion gene

“…Serum FSH concentrations were measured by immunofluorometric assay as described earlier (van Casteren et al, 2000). Progesterone and testosterone concentrations were measured by RIA from diethyl ether extracts as described earlier (Huhtaniemi et al, 1985;Vuorento et al, 1989). Concentrations of inhibins A and B were measured by dimeric inhibins A and B immunoassays according to the instructions of the manufacturer (Oxford Bio-Innovation, Serotec, Oxford, UK).…”