Effects of Medroxyprogesterone and Estradiol on the Recovery of Spermatogenesis in Irradiated Rats

Abstract

Suppression of intratesticular testosterone (ITT) levels is required for spermatogenic recovery in rats after irradiation, but maintenance of peripheral testosterone (T) levels is important for many male functions. Considering the preservation of peripheral T while suppressing ITT, we tested the effects of a combination of a progestin, medroxyprogesterone acetate (MPA), plus T on spermatogenic recovery after irradiation, and compared its effects to those of T alone or T combined with estradiol (E2). Rats were given testicular irradiation (6 Gy) and treated during wk 3-7 after irradiation with MPA + T, or the individual steroids with or without GnRH antagonist (GnRH-ant), or GnRH-ant alone, or T + E2. Whereas GnRH-ant alone stimulated differentiation in 55% of tubules 13 wk after irradiation compared with 0% in irradiated-only rats, the addition of MPA reduced the percentage of tubules showing differentiation to 18%. However, T or MPA alone or the combination of the two induced germ cell differentiation in only 2-4% of tubules. In contrast, E2 stimulated differentiation in 88% of tubules, and T combined with E2 still resulted in differentiation in 30% of tubules. Although both MPA and E2 suppressed ITT levels to approximately 2% of control (2 ng/g testis), MPA was a less effective stimulator of spermatogenic recovery than E2 or GnRH-ant alone. MPA's function as a weak androgen was likely responsible for inhibiting spermatogenic recovery, as was the case for all other tested androgens. Thus, for clinical protection or restoration of spermatogenesis after radiation or chemotherapy by suppressing T production, MPA, at least in the doses used in the present study, is suboptimal. The combination of an estrogen with T appears to be most effective for stimulating such recovery.

Follicle-Stimulating Hormone-Independent Functions of Primate Sertoli Cells: Potential Implications in the Diagnosis and Management of Male Infertility

“…However, lack of E 2 or estrogen receptor activity is associated with infertility (17,18), and injection of lactate in cryptorchid testes of adult rats significantly augments sperm production (39), lending support to the notion that lactate and E 2 are essential for spermatogenesis. In a recent study, E 2 has been demonstrated to induce Gc differentiation in 88% of seminiferous tubules of irradiated rats (40).…”

Ceramides and Sphingomyelins with High Proportions of Very Long-chain Polyunsaturated Fatty acids in Mammalian Germ Cells

“…Ischemia was induced by a clockwise 720°torsion applied to the spermatic cord by open surgery (21) for 1 h, followed by a return to the natural position to allow for reperfusion of the tissue. Exposure of testes to ionizing radiation was performed according to published procedures and doses (22,23). Briefly, anesthetized animals were irradiated locally at a distance of 100 cm with a single total dose of 6.5 gray of X-rays produced by a linear accelerator.…”

Estrogen-Regulated Genes in Rat Testes and Their Relationship to Recovery of Spermatogenesis after Irradiation1

“…During studies of regulation of spermatogenic recovery in rats after gonadotoxic therapy for cancer, we found that estrogen stimulated the recovery of spermatogonial differentiation [1][2][3], but the mechanism of action was not identified. Estrogens indeed have widespread effects on spermatogenesis and male reproduction, but those effects and the mechanisms involved are quite complex [4,5].…”