The effect of a null mutation in the follicle-stimulating hormone receptor gene on mouse reproduction.
To investigate further brain-pituitary-gonadal interrelationships we have generated mice in which the gene encoding the FSH receptor has been disrupted. Female FSH receptor knockout (FSHRKO) mice were infertile. The ovaries were significantly reduced in size, with follicular development arrested at the preantral stage, but there was evidence of stromal hypertrophy. The vagina was imperforate, and the uterus was atrophic. There was no response to administration of PMSG. Inhibins A and B were undetectable in both the serum 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 administration in FSHRKO female mice suppressed serum LH levels to those seen in control mice, whereas FSH levels were reduced by only 50%. Male FSHRKO mice were fertile, although testis weight was significantly reduced. However, testicular inhibin A and B concentrations did not differ from those in normal 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 these hormones. In conclusion, ovarian follicular development cannot progress beyond the preantral stage without FSH. In the absence of mature follicles ovarian estrogen remains low, and consequently accessory sex tissue growth and negative feedback regulation of gonadotropin secretion are severely compromised. In the male, however, inability to respond to FSH does not impair fertility, although testicular weight is reduced, and feedback regulation of pituitary gonadotropins and intratesticular paracrine interactions may be disturbed.
Abel
M H
MH
Department of Human Anatomy and Genetics, University of Oxford, United Kingdom. margaret.abel@anat.ox.ac.uk
Wootton
A N
AN
Wilkins
V
V
Huhtaniemi
I
I
Knight
P G
PG
Charlton
H M
HM
D000818:Animals; D019281:Dimerization; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006064:Gonadotropins, Equine / Q000494:pharmacology; D007265:Inhibins / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009929:Organ Size; D010641:Phenotype; D011962:Receptors, FSH / Q000235:genetics* / Q000502:physiology; D012098:Reproduction / Q000235:genetics*; D014621:Vagina / Q000002:abnormalities
D006064:Gonadotropins, Equine; D011962:Receptors, FSH; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone