Inhibition of Canine Spermatogonial Mitosis with Follicle Regulatory Protein

Abstract

Evidence was found that the Graafian follicle produces and secretes a hormonelike protein, referred to as follicle regulatory protein (FRP), which affects the responsivity of other follicles to gonadotropin stimulation. Since a similar material was identified in homogenates of bull testes, we evaluated the effects of FRP on the histology of seminiferous epithelium by its systemic injection into normal dogs. Mongrel dogs were injected IM with 5 mg of FRP for 17 consecutive days. The seminiferous epithelium was evaluated by light microscopy and divided into eight stages according to Foote. The relative frequency of stage 4 was significantly less in the FRP-treated than in the control group, but that of stage 7 was significantly greater in the FRP-treated group. The ratios of type B/type A spennatogonia for control and FRP-treated groups for stages 6-8 were 1.5, 5.8, 2.4, and 1.6, 4.3, 1.6, respectively. The tubular diameters of stages 6 and 7 were significantly different between the two groups. The numbers of tubules containing spermatogonial divisions were significantly decreased at stages 2 + 3 and stages 6+7 in the FRP-treated group. A clear decrease in the number of tubule profiles with spermatogonial divisions was present at stages 6 and 7 in the FRP-treated testis. Taken together, these findings suggest that FRP inhibits spermatogonial transformation of type A into type B.

Immunocytochemical localization of follicle regulatory‐protein (FRP) in testis

“…Biological effects of FRP are not limited to the female gonads. In the intact dogs, FRP causes a decrease in spermatogenesis by reducing proliferation of spermatogonia (Fujimori et al, 1986). Similar inhibitory effects were also noted in male rats treated with various dosages of FRP (Tsutsumi et al, 1987a,b).…”

Purification of Follicular Regulatory Protein: Possible Plasminogen Identity

“…Many functions of FRP have been proposed, as reviewed by diZerega et al (6). FRP is believed to (a) inhibit microsomal aromatase activity and microsomal 3B-hydroxysteroid dehydrogenase activity in vitro (12)(13), (b) inhibit thecal aromatase activity from large and medium-sized follicles of pigs (16,17), (c) alter the production and secretion of progesterone from granulosa cells in vitro (14 -15), (d) inhibit the increase in ovarian weight and serum estradiol levels in hypopophsectomized, immature, diethylstilbestrol-treated female rats (2), (e) inhibit granulosa cell and placental microsomal aromatase activity (3-7), (f) delay follicular maturation in spontaneously cycling monkeys (8), (g) inhibit FSH induction of LH/hCG receptors in porcine granulosa cells (9), (h) associate with perifollicular neovascularization during folliculogenesis (10,11), (i) inhibit spermatogonial transformation from type A into type B in vivo (18), (j) disrupt seminiferous epithelial function and reduce sperm production after injection of FRP into rats (19 -21), (k) alter follicular steroid secretion and thecal morphology (24), (l) fluctuate during the menstrual cycle (25,26), (m) increase in persons with reproductive disorders (23), and finally, using the monoclonal antibody 1A8D5, FRP was suggested as a novel marker for granulosa cell cancer patients (27) and inhibit ovarian cancer cell proliferation (22). In addition monoclonal antibody 1A8D5 was also used to localize FRP in the granulosa cells of porcine follicles (28,29) and testes (30).…”