PARENT SESSION
SLIDE SESSION 18: HORMONE RECEPTORS, STEROID HORMONE ACTION
Chairs: Terry Nett, Leslie Heckert, Dustin Vale-Cruz (Trainee)
Univ Ottawa-Arts Hall 257
1:30 PM-3:30 PM

KNOCKOUT OF LH RECEPTORS REVEALED REPRODUCTIVE ABNORMALITIES IN OLDER HETEROZYGOUS FEMALE SIBLINGS.

Mishra, Suresh¹, Lei, Zhenmin¹, Foltz, Mark¹, Rao, Ch.¹, ¹

ABSTRACT- We recently knocked out LH receptors by gene targeting in embryonic stem cells. While the loss of LH signaling was not lethal, the null animals were infertile with a marked underdevelopment of external and internal genitalia. Heterozygous female siblings, on the other hand, were not distinguishable from wild-type littermates until about two months of age. As they grew older, however, heterozygous animals stopped cycling and appeared to reach reproductive senescence earlier than wild-type siblings. Moreover, a subpopulation became heavy with an accumulation of large amounts of visceral fat. While ovarian weight remained similar, uterine and oviductal weights increased when compared with wild-type siblings. The uteri contained several fluid-filled cysts and various-sized tumors. Opening the uterine cavity revealed the presence of numerous endometrial tumors in virtually every heterozygous animal. Histological examination revealed a marked dilation of uterine blood vessels, angiogenesis, glandular and stromal hyperplasia, an increase in glandular/stromal ratio. The immunostaining for proliferative cell nuclear antigen indicated extensive glandular and stromal-cell proliferation. While the molecular basis of these changes remains to be investigated in heterozygous animals, present findings imply that an inactivation of a LH receptor gene allele may lead to early reproductive senescence, adiposity and endometrial cancer.

KEY WORDS: LH receptor knockout, reproductive senescence, endometrial cancer, adiposity