R Rappaport

The purpose of the present study was to report on gonadotropin function and puberty of a large group of children treated by cranial irradiation for cranial and neck tumors and medulloblastoma. Forty-five children of pubertal age were investigated. The mean interval time since radiation was 5 2/12 yr. Gonadotropin and gonadal function were evaluated by clinical criteria, plasma sex steroids, and plasma LH and FSH responses to LRH. Puberty was complete or progressing normally in 31 cases and was abnormal in 14 cases. Severe gonadotropin deficiency, with lack of or slow progression of puberty and decreased LH and FSH responsiveness to LRH, was observed in 5 cases; 2 of these had moderately elevated plasma PRL levels. Secondary amenorrhea or lack of pubertal progression was found in 5 other cases. GH deficiency was associated with gonadotropin deficiency in 9 of these 10 cases. Adrenal function, estimated by basal dehydroisoepiandrosterone, dehydroisoepiandrosterone sulfate, and estrone, was normal according to pubic hair stages. In conclusion, complete or partial gonadotropin deficiency can be the consequence of cranial irradiation in children receiving 6000 rads or less. It is usually associated with GH deficiency. The site of the damage on the pituitary gland or the hypothalamus remains to be demonstrated.

In order to study the effect of vitamin D3, and some of its metabolites on cartilage, chondrocytes from the proliferative zone of rabbit growth plate cartilage were isolated and grown in culture. The 35SO4 incorporation into proteoglycans extracted from the cells or into macromolecules obtained after dialysis of the culture medium was evaluated in the presence of vitamin D3, synthetic 25-hydroxycholecalciferol (25-(0H)D3), 24,25- and 1,25-dihydroxycholecalciferols (24,25-(OH)2D3 and 1,25-(OH)2D3). At concentrations between 2.4 X 10-l3 M and 2.4 x 10-10 M, 24,25-(OH)2D3) was stimulatory. l,25-(OH)2D3 was also active at 2.4 X 10-11 M and 1.2 X 10-10 M concentrations. Higher concentrations of 25-(OH)2D3) (2.5 x 10-8 M) were necessary to obtain a similar response. In contrast, vitamin D3 was inactive at concentrations ranging from 10-14 M-10-7 M. A polar derivative was obtained after incubation of chondrocytes or cartilage tissue with 25-(OH)2D3, and was presumed to be 24,25-(OH)2D3 This cartilage polar derivative was found to be equipotent to both synthetic and biosynthetic 24,25-(OH)2D3 in the cultured chondrocytes bioassay system. (Endocrinology102: 1269, 1978)