The effect of a null mutation in the follicle-stimulating hormone receptorgene on mouse reproduction

To investigate further brain-pituitary-gonadal interrelationships we have g enerated mice in which the gene encoding the FSH receptor has been disrupte d. Female FSH receptor knockout (FSHRKO) mice were infertile. The ovaries w ere significantly reduced in size, with follicular development arrested at the preantral stage, but there was evidence of stromal hypertrophy. The vag ina was imperforate, and the uterus was atrophic. There was no response to administration of PMSG. Inhibins A and B were undetectable in both the seru m and gonads. Compared with those in control animals, serum concentrations of FSH and LH were significantly elevated in mutant females. The pituitary content of FSH, but not LH, was also significantly elevated. Estrogen admin istration in FSHRKO female mice suppressed serum LH levels to those seen in control mice, whereas FSH levels were reduced by only 50%. Male FSHRKO mic e were fertile, although testis weight was significantly reduced. However, testicular inhibin A and B concentrations did not differ from those in norm al littermates. Serum levels of FSH and LH were elevated in the null mutant male mice, whereas no differences were found in the pituitary content of t hese hormones. In conclusion, ovarian follicular development cannot progres s beyond the preantral stage without FSH. In the absence of mature follicle s ovarian estrogen remains low, and consequently accessory sex tissue growt h and negative feedback regulation of gonadotropin secretion are severely c ompromised. In the male, however, inability to respond to FSH does not impa ir fertility, although testicular weight is reduced, and feedback regulatio n of pituitary gonadotropins and intratesticular paracrine interactions may be disturbed.