Hypopituitarism results in a cessation of bone growth, a decrease in bone formation and cancellous bone volume in humans and animals, mechanism still remaining unclear. Growth hormone (GH) replacement to the hypophysectomized(HX) young rats restored the growth of long bone, but only partially prevented the loss of cancellous bone volume. This study is to examine the efficacy of GH with or without 17b-estradiol(E) on cortical and cancellous bones of the HX rats. 2 month old female Sprague-Dawley rats, were divided into basal(B), age matched intact control(AMC), HX, HX+GH(2.25mg/kg/day), HX+E(100ug/kg/wk) and HX+GH+E groups with 10 rats in each group. The basal group was sacrificed at two months of age and the remaining after 3 weeks of treatment. Prior to sacrifice, they were labeled with flurochrome chemicals at fixed time intervals for the estimation of mineral apposition rate(MAR) and bone formation rate(BFR). Our results showed that HX rats had atrophy of adrenal glands and uterus, cessation of systemic growth (tibial length, body and muscle weight) and a decrease in tibial and the 6th lumbar vertebral (L6) dry weight as compared to the B and AMC groups. The bone histomorphometry revealed that HX induced a decrease in periosteal MAR(0.2±0.4um/d vs AMC:3.1±0.5, P<0.05), periosteal BFR(1.4 ± 4.6um3/um2/d vs AMC:259±57, P<0.05) and a loss of cancellous bone (2.2±1.3% vs AMC: 14.5±3.4, P<0.05). GH administration to the HX rats restored systemic and bone growth, increased tibial (346±28mg vs HX:291±22, P<0.05) and L6(140±18mg vs HX: 120±13, P<0.05) dry weight, periosteal BFR(127±20um3/um2/d vs HX:1.4±4.6, P<0.05), and decreased cancellous bone loss (5.8±3.0% vs HX:2.2±1.3, P<0.05). The dosage of E used, prevented the cancellous bone loss in ovariectomized rats, but did not significantly prevent the cancellous bone loss in HX rats(4.0±3.0% vs HX:2.2±1.3,). E administration prevented uterine atrophy, but did not affect the systemic growth, bone growth or the periosteal BFR in the HX rats. The combined use of GH and E prevented the uterine atrophy, and increased the cancellous bone (7.0±2.6%) as compared to the GH treatment alone. In conclusion, this study clearly demonstrates the beneficial effect of E is diminished in HX rats and GH replacement is unable to restore the protection, however, the combined GH and E administration to HX rats has an additive effect to protect the bone mass, as compared to GH treatment alone.
