Altered ovarian function affects skeletal homeostasis independent of the action of follicle-stimulating hormone.
Osteoporosis is a leading public health problem. Although a major cause in women is thought to be a decline in estrogen, it has recently been proposed that FSH or follitropin is required for osteoporotic bone loss. We examined the FSH receptor null mouse (FORKO mouse) to determine whether altered ovarian function could induce bone loss independent of FSH action. By 3 months of age, FORKO mice developed age-dependent declines in bone mineral density and trabecular bone volume of the lumbar spine and femur, which could be partly reversed by ovarian transplantation. Bilateral ovariectomy reduced elevated circulating testosterone levels in FORKO mice and decreased bone mass to levels indistinguishable from those in ovariectomized wild-type controls. Androgen receptor blockade and especially aromatase inhibition each produced bone volume reductions in the FORKO mouse. The results indicate that ovarian secretory products, notably estrogen, and peripheral conversion of ovarian androgen to estrogen can alter bone homeostasis independent of any bone resorptive action of FSH.
Gao
Jianjun
J
Calcium Research Laboratory, McGill University Health Centre, 687 Pine Avenue West, Montreal, Quebec, Canada.
Tiwari-Pandey
Rashmi
R
Samadfam
Rana
R
Yang
Yinzhi
Y
Miao
Dengshun
D
Karaplis
Andrew C
AC
Sairam
M Ram
MR
Goltzman
David
D
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D015519:Bone Density / Q000235:genetics; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010024:Osteoporosis / Q000473:pathology; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology* / Q000503:physiopathology / Q000637:transplantation; D011962:Receptors, FSH / Q000235:genetics
D000728:Androgens; D011962:Receptors, FSH; D005640:Follicle Stimulating Hormone