The effect of bovine growth hormone on growth of mammary tumors in hypophysectomized rats

Bovine growth hormone has been shown to be effective in promoting growth of mammary tumors in hypophysectomized rats treated with 7, 12-dimethylbenzathracene.     

Cell kinetics of the growth plate in hypophysectomized rats treated with growth hormone and thyroxine

Summary The cell production in the growth plate of the proximal tibia was calculated in hypophysectomized rats given growth hormone and/or thyroxine from values of longitudinal bone growth determined with oxytetracycline and the size of degenerative cells in the growth plate.The changes in longitudinal bone growth induced by thyroxine and growth hormone in hypophysectomized rats were found to be predominantly caused by changes in the cell production, whereas the changes in the size of the degenerative cells were minor. The stimulation of cell production by growth hormone was dependent on the dose and the administration period. Thyroxine was found to stimulate the cell production up to an optimum dose of thyroxine.     

Zinc deficiency inhibits the direct growth effect of growth hormone on the tibia of hypophysectomized rats

The effect of zinc deficiency on the direct-growth effect of growth hormone (GH) on tibia growth in hypophysectomized rats was studied. There were three dietary groups. Zinc deficient (ZD) group (0.9 mg/kg diet), control (C) group (66 mg/kg diet) and zinc adequate pair fed (PF) group (66 mg zinc/kg diet). All rats in each group received local infusion of recombinant human-growth hormone (hGH) (1 Μg/d), except for half of the animals in the control group, which were sham-treated, receiving vehicle infusion only. The substances were infused continuously for 13 d by osmotic minipumps through a catheter implanted into the right femoral artery. Food intake was lower and body weight loss was greater in ZD, and PF animals compared with C animals (p < 0.001). Tissuezinc concentration and plasma alkaline-phosphatase activity were decreased (p < 0.05) by dietary-zinc deficiency. GH infusion increased the tibial-epiphyseal width of the treated right limb, but not of the noninfused left limb in C and PF animals. However, in ZD rats, no difference was found between the infused and the noninfused limbs. These results demonstrate that zinc deficiency inhibits the direct-growth effect of GH on long-bone growth.     

Influence of growth hormone on accretion of bone mass

Growth hormone (GH) exerts important influences on bone metabolism during lifespan. During childhood, GH is a major determinant of acquisition of bone mass and in adult life, GH partly determines the rate of bone remodelling and therefore influences maintenance of bone mineral density (BMD). Insights into the importance of GH in these respects may be obtained by studies of BMD and indices of bone remodelling in GH deficiency (GHD) of adult-onset and childhood-onset. Adult-onset GHD, usually accompanied by other features of hypopituitarism, may be associated with osteopenia and an increased fracture risk. Postulated mechanisms include GHD and gonadal steroid deficiency of unknown duration; glucocorticoid and thyroxine replacement do not appear to exert a major role. GH replacement in adult-onset GHD results in an early increment in indices of bone remodelling which persists for up to 5 years; BMD increases by 0.5-1.0 SD in males and stabilizes in females over this time period. In adolescents with GHD who traditionally discontinue GH at completion of linear growth, BMD is substantially lower than peak bone mass for a young adult population. Studies addressing the effects of continuation of GH after achievement of final height are currently underway and will provide insights into the possible need to continue GH into adult life. Such studies may confirm a role for GH in promoting continued accrual of bone mass and thereby demonstrate that cessation of GH at achievement of final height, by limiting peak bone mass, may predispose to clinically significant osteoporosis in later life. In addition to the potential importance of GH for achievement of peak bone mass, there may be a superimposed accelerated loss of BMD with advancing age similar to the situation observed in adult-onset GHD. To date, this has been difficult to assess in adult GHD of childhood-onset because the relative contributions of low peak bone mass and increased loss of bone in later life could not be distinguished.     

Comparison of effects of prolactin and growth hormone on adrenal 5alpha-reductase in hypophysectomized rats.

Adrenal 5alpha-reductase activity was measured in female rats 0, 2, 5, and 6 days after hypophysectomy. Enzyme activity increased progressively exhibing a 35-fold elevation at 6 days. The effects of high (250 mug/100 g of body wt), intermediate (25 mug/100 g of body wt), and low (2.5 mug/100 of body wt) daily doses of bovine prolactin and bovine growth hormone were compared at 2 and 5 days posthypophysectomy. At 2 days, enzyme activity was partially inhibited by the high and intermediate doses of prolactin and not affected by growth hormone. At 5 days all doses of prolactin were inhibitory, whereas enzyme activity was suppressed only by the high dose of growth hormone. With a given dose of hormone, the amount of suppression of enzyme activity is greater at 5 days than at 2 days posthypophysectomy. In 5-day hypophysectomized rats the inhibitory effects of prolactin and growth hormone were additive. It is concluded that: (i) hormonal sensitivity and responsiveness of the adrenal reductase pathway increases with duration of pituitary ablation; (ii) the reductive pathway is more sensitive to the effects of prolactin than growth hormone; and (iii) the effects of growth hormone and prolactin on reductase activity are mediated via different mechanisms, as suggested by the additive effects of individual hormones.     

Growth and growth hormone in children after bone marrow transplantation

Growth and growth hormone (GH) were investigated every year in 24 children after allogeneic bone marrow transplantation (BMT) for severe aplastic anemia (SAA) or leukemia. Conditioning included total body irradiation (TBI) in all cases of leukemia. The young leukemic children grew poorly. At 4 years after BMT, the mean standard deviation score for attained height had decreased from 0 to -1.73. GH deficiency was diagnosed with provocation tests. Three years after BMT, 10/18 children had a subnormal response. Ten children were further investigated with 24-hour GH profiles. Children with SAA had normal growth and GH levels. TBI seemed to be the major factor responsible for impaired growth.     

Equine luteinizing hormone possesses follicle-stimulating hormone activity in hypophysectomized female rats

The ability of equine luteinizing hormone (eLH) to promote follicular growth and maturation in hypophysectomized rats has been assessed. A single injection of equine LH has been shown to promote the growth of a large number of antral and preovulatory follicles. In addition, equine LH markedly increased serum estrogen levels and uterine weight. Furthermore, equine LH, like equine chorionic gonadotropin (eCG; PMSG) was able to significantly enhance the incorporation of [3H]thymidine into ovarian DNA, an activity shown to be specific to hormones having follicle-stimulating hormone (FSH) activity. Equine LH treated with an FSH antibody immunoaffinity column to remove any possible contamination still exhibited the above activity, demonstrating that the FSH activity is intrinsic to the eLH molecule. Equine LH has also been shown to be capable of inducing LH receptors in granulosa cells of ovaries of hypophysectomized rats, an activity specific to FSH-like hormones. From the doses required of eLH and the degree of response observed, it is concluded, however, that eLH in the hypophysectomized rat is less active than eCG as an FSH.