This project proposes to explore the relationship between growth hormone (GH) and sulphation factor (SF) with specific respect to the liver as a probable source of SF. Three specific questions are to be approached: Is SF produced by the liver in response to GH? What are the control mechanisms involved? Is cessation of longitudinal skeletal growth related to altered hepatic response to GH? The first of these objectives will be approached by incubation of liver slices, perfusion of intact livers, and measurement of the response of hepatectomized animals to GH. Control mechanisms involved will be studied by adding agents to incubation and/or perfusion media. These will include insulin, thyroxin, estrogen, testosterone, and cortisone. Since SF is assayed by measuring the synthetic capabilities of hypophysectomized rat cartilage, addition of these agents, singly and in combination to media before and after incubation or perfusion will demonstrate whether they have an effect on cartilage synthesis and whether this effect is a direct effect on cartilage, enhancement of SF effect on cartilage, or altered responsiveness of the liver to GH. The third question relates to the cessation of longitudinal skeletal growth of humans. This cessation could be due to diminished GH release, decreased SF production by the liver of diminished end-organ response. There is evience to suggest that both GH and SF levels in humans are rather constant during adolescence. End-organ failure is, therefore, suggested but has not been demonstrated. This question will be approached by quantitating the response to SF of human epiphyseal plate cartilage. If end-organ variability is demonstrated and rib and limb cartilage are similar, a safe and useful measure in the clinical assessment of growth perturbations will be available in the form of rib cartilage biopsy.