Restoration of bone mass in hpg mouse by preoptic area grafting.

Hereditary hypogonadism in the hpg mouse, caused by a deletion mutation in the gonadotropin-releasing hormone (GnRH) gene, is associated with sterility, absent ovarian development, and undetectable circulating sex steroids. Eight-month-old female hpg mice had a significantly reduced bone mineral density (BMD) at the lumbar spine, femur, and tibia. In addition, the mice showed significant reductions in liver and kidney weight, with virtually nonexistent ovaries.

Expression of estrogen receptor {alpha} in the anteroventral periventricular nucleus of hypogonadal mice.

Gonadotropin-releasing hormone-1 (GnRH-1) neurons play critical roles in the development and maintenance of reproductive function in all vertebrates. Due to a truncation in the GnRH-1 gene, hypogonadal (hpg) mice are unable to synthesize GnRH-1 and are infertile. These animals develop in the complete absence of exposure to gonadal steroid hormones, making them an interesting model for understanding brain sexual differentiation and dimorphism.

TSH is a negative regulator of skeletal remodeling.

The established function of thyroid stimulating hormone (TSH) is to promote thyroid follicle development and hormone secretion. The osteoporosis associated with hyperthyroidism is traditionally viewed as a secondary consequence of altered thyroid function. We provide evidence for direct effects of TSH on both components of skeletal remodeling, osteoblastic bone formation, and osteoclastic bone resorption, mediated via the TSH receptor (TSHR) found on osteoblast and osteoclast precursors.

Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice.

We describe the effects of the overexpression of noggin, a bone morphogenetic protein (BMP) inhibitor, on osteoblast differentiation and bone formation. Cells of the osteoblast and chondrocyte lineages, as well as bone marrow macrophages, showed intense beta-gal histo- or cytostaining in adult noggin+/- mice that had a LacZ transgene inserted at the site of noggin deletion. Despite identical BMP levels, however, osteoblasts of 20-month-old C57BL/6J and 4-month-old senescence-accelerated mice (SAM-P6 mice) had noggin expression levels that were approximately fourfold higher than those of 4-month-old C57BL/6J and SAM-R1 (control) mice, respectively.