Effects of unilateral arterial infusion of GH and IGF-I on tibial longitudinal bone growth in hypophysectomized rats

Summary We have studied the effect of local arterial infusion of bacterially produced human growth hormone (hGH), insulinlike growth factor I (IGF-I), or pituitary-derived ovine prolactin (oPRL) on longitudinal bone growth of hypophysectomized rats. The substances were infused during a 14-day period by osmotic mini-pumps through a catheter which was implanted into the femoral artery of one hindlimb. Longitudinal bone growth was measured by the intravital marker tetracycline. Infusion of 1 μg hGH per day stimulated bone growth only of the treated limb and not of the uninfused contralateral limb. Infusion of 10 μg hGH per day also stimulated unilateral longitudinal bone growth, but the uninfused contralateral limb also showed a significant growth response, probably because local administration of GH at this dose caused a significant elevation of GH in the systemic circulation. As a result, the differential growth response between the GH-treated and untreated limbs decreased compared to rats that were infused with 1 μg hGH per day. Unilateral arterial infusion of 5 μg human IGF-I or 10 μg oPRL per day did not produce a significant growth response. The results of the present study confirm the observation by Schlechter and co-workers [9, 16], who demonstrated that unilateral arterial infusion of GH maintained tibial cartilage width following hypophysectomy in the rat. The results of Schlechter and co-workers and the results of the present study show that GHin vivo stimulates epiphyseal cartilage growth directly. However, an increased local production of insulinlike growth factors is probably of importance for the expression of the direct effect of GH on longitudinal bone growth. The present results do not completely rule out the possibility that insulinlike growth factors in the circulation might have the growth plate as a target organ.