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PubMed1999

Role of FSH in male gonadal function.

The production of male gametes depends on the concerted action of the two gonadotropins FSH and LH on the testis. The action of LH is mediated through the production of testosterone by the Leydig cells. Since male germ cells possess neither FSH nor androgen receptors, the action of FSH and testosterone occurs through the Sertoli cells. Although the precise function of these two hormones remains elusive, the existing evidence suggest that both FSH and testosterone are able to stimulate all phases of spermatogenesis. In the male FSH is required for the determination of Sertoli cell number, and for induction and maintenance of normal sperm production. The crucial role of FSH in male gonadal function has been clearly illustrated by the discovery of a patient with an activating mutation of the FSH receptor. This patient had been hypophysectomized because of a pituitary tumor and, under testosterone substitution was unexpectedly fertile in spite of undetectable serum gonadotropin levels and had fathered three children. In this patient we could demonstrate a heterozygous activating mutation of the FSH receptor which resulted in cAMP production independent of FSH stimulation. This finding represents the first description of an activating mutation of the FSH receptor and demonstrates that FSH alone maintains spermatogenesis in man. On the other hand, the effects of the lack of FSH action are unclear. Among five men with a homozygous inactivating mutation of the FSH receptor only one was infertile and spermatogenesis was variably affected in the others. However, serum inhibin B values in these men were not completely suppressed and serum FSH levels were only moderately elevated, indicating the possibility that FSH receptor function was not completely abolished by the mutation. Elimination of FSH action is a prerequisite to suppress completely spermatogenesis for contraceptive purposes, while administration of both LH and FSH is necessary to induce sperm production in patients with hypogonadotropic hypogonadism. Experimental immunization of male monkeys against FSH markedly reduced germ cell proliferation and even induced infertility. At the cellular level, FSH stimulates the cAMP-dependent activation of protein kinase A in Sertoli cells, but the molecular mechanism of FSH action is poorly understood. In the primate, the gonadotropin withdrawal achieved by administration of a GnRH antagonist leads to a premeiotic arrest of germ cell proliferation, probably due to inhibition of the mitotic division of A-pale spermatogonia. Therefore, FSH might be the prime inducer of spermatogonial proliferation, while the successive maturation process could proceed independently of FSH. In summary, clinical and experimental evidence support the concept of an irreplaceble role of FSH in the primate. Only the combination of FSH and testosterone, however, supports a qualitatively and quantitatively fully normal spermatogenesis.

Animals↗
PubMed2004

FSH different regimes affect the developmental capacity and cryotolerance of embryos derived from oocytes collected by ovum pick-up in donor sheep.

The objective of the present study was to compare the developmental capacity of sheep oocytes obtained by OPU after two different ovarian stimulations, and cryotolerance to vitrification procedures of in vitro derived embryos after in vitro maturation, fertilisation and culture of these oocytes. Sheep were divided into three groups: (A) no treatment (control); (B) constant doses of FSH (FSH-c); (C) decreasing doses of FSH (FSH-d). Ovine groups FSH-c and FSH-d were synchronised by the insertion of intravaginal sponges left in situ for 7 days; FSH (total dose: 96IU) was administered in four doses given every 12h starting on Day 5. Twelve hours after the last FSH administration oocytes were collected by OPU technique. The control group showed a significantly lower number ( P<0.05 ) of follicles (166) than FSH-c (294) and FSH-d (317) groups, while the number of follicles >5mm was significantly higher ( P<0.01 ) in FSH-d group, showing that this protocol stimulates the growth of a different follicle population compared to FSH-c group. The control group showed a higher number of <2mm follicles ( P<0.01 ). We did not find any difference in oocyte quality between the three groups and therefore the percentage of discarded oocytes was similar. No significant differences were found between control, FSH-c and FSH-d groups in terms of maturation (90.9, 85.7 and 87.7%, respectively) and fertilisation rates (75.2, 80.9 and 83.7%, respectively) while a significantly higher ( P<0.01 ) blastocyst rate was observed in the FSH-c group than in the FSH-d and control groups (20.4% versus 11.8 and 13.7%, respectively). After vitrification, warming and 72 h in vitro culture, the hatching rate was significantly higher ( P<0.01 ) in the control (87.5%) and FSH-c (90.5%) groups than in the FSH-d group (66.7%). Control and FSH-c groups showed a significantly higher ( P<0.001 ) number of total cells than FSH-d group ( 217.6+/-26.5 and 203.0+/-33.2 versus 147.5+/-20.2 ), while no differences were observed in ICM cell rates in the control ( 35.6+/-3.8 ), FSH-c ( 37.1+/-4.6 ) and FSH-d ( 36.6+/-6.7 ) groups. These results indicate that donor sheep stimulated with FSH-c produced better quality oocytes and blastocysts showing better cryotolerance than ewes given the decreasing doses treatment.

Animals↗