Fp. Zhang et al., Normal prenatal but arrested postnatal sexual development of luteinizing hormone receptor knockout (LuRKO) mice, MOL ENDOCR, 15(1), 2001, pp. 172-183
To study further the role of gonadotropins in reproductive functions, we ge
nerated mice with LH receptor (LHR) knockout (LuRKO) by inactivating, throu
gh homologous recombination, exon 11 on the LHR gene. LuRKO males and femal
es were born phenotypically normal with testes, ovaries, and genital struct
ures indistinguishable from their wild-type (WT) littermates. Postnatally,
testicular growth and descent, and external genital and accessory sex organ
maturation, were blocked in LuRKO males, and their spermatogenesis was arr
ested at the round spermatid stage. The number and sire of Leydig cells wer
e dramatically reduced. LuRKO females also displayed underdeveloped externa
l genitalia and uteri postnatally, and their age of vaginal opening was del
ayed by 5-7 days. The (-/-) ovaries were smaller, and histological analysis
revealed follicles up to the early antral stage, but no preovulatory folli
cles or corpora lutea. Reduced gonadal sex hormone production was found in
each sex, as was also reflected by the suppressed accessory sex organ weigh
ts and elevated gonadotropin levels. Completion of meiosis of testicular ge
rm cells in the LuRKO mates differs from other hypogonadotropic/cryptorchid
mouse models, suggesting a role for FSH in this process. In females, FSH a
ppears to stimulate developing follicles from the preantral to early antral
stage, and LH is the stimulus beyond this stage. Hence, in each sex, the i
ntrauterine sex differentiation is independent of LH action, but it has a c
rucial role postnatally for attaining sexual maturity. The LuRKO mouse is a
close phenocopy of recently characterized human patients with inactivating
LHR mutations, although the lack of pseudohermaphroditism in LuRKO males s
uggests that the intrauterine sex differentiation in this species is not de
pendent on LH action.