Inhibition of growth of the transplantable rat chondrosarcoma by analogs of hypothalamic hormones

Abstract

The Swarm chondrosarcoma is a hormone-responsive tumor whose growth is dependent on growth hormone, somatomedins, and glucocorticoids. Our previous work showed that partial functional hypophysectomy can be achieved by chronic administration of the luteinizing hormone-releasing hormone (LH-RH) analog LH-RH, which lowers blood levels ofLH and follicle-stimulating hormone. We have also demonstrated that somatostatin (SS)-28 or analogs of SS-14 depress serum prolactin, growth hormone, and corticotropin (ACTH) levels. Consequently, we investigated the effect of subcutaneous injection of these analogs on the growth of Swarm chondrosarcoma 3 days after transplanting it into male Sprague-Dawley rats. At autopsy, tumor volume was measured and tumors and various organs were weighed. In rats treated with three different analogs of (GH) and cortisone also act synergistically to stimulate the growth of this chondrosarcoma in hypophysectomized rats. In addition, they were able to show that chondrosarcomas respond, in vitro, to GH-dependent serum growth factors (somatomedins) and insulin by increases in amino acid transport and macromolecule synthesis (6). They concluded that the growth ofthe chondrosarcoma was mediated through somatomedins and by glucocorticoids. Recent biochemical data indicate that somatomedins stimulate both RNA and protein synthesis in chondrosarcoma tissue (7).Repeated administration of agonistic luteinizing hormonereleasing hormone (LH-RH) analogs leads to decreased responsiveness of the pituitary gland and inhibition of gonadal steroid secretion (8, 9). These paradoxical inhibitory effects induced by prolonged administration of LH-RH agonists have been linked with the regression of hormone-dependent mammary and prostate carcinomas in rats (10, 15).We have previously shown that chronic administration of[DTrp6]LH-RH, an agonist of LH-RH, significantly inhibited the growth of two different types of transplantable rat prostate tumors (14). In another study, we demonstrated that prolonged treatment with antagonistic analogs ofLH-RH can also suppress the growth of rat prostate tumors (15). Our group extended these findings to men and provided evidence for tumor growth inhibition in patients with prostatic carcinoma treated with LH-RH agonists (16). These studies showed that chronic administration ofLH-RH agonists or antagonists can inhibit the growth of sex steroid-dependent tumors by suppressing both pituitary and gonadal functions. The investigations with analogs of hypothalamic hormones were then extended to pituitary tumors (17). We demonstrated that chronic administration of agonistic and antagonistic LH-RH analogs or somatostatin (SS) analogs to rats bearing the estrogen-dependent prolactin-and corticotropin-secreting pituitary tumor 7315a significantly decreased growth, volume, and weight of this tumor (17).Since GH-dependent somatomedins and insulin play a vital part in growth of the Swarm chondrosarcoma, it became apparent that analogs of

Growth hormone-releasing hormone: An autocrine growth factor for small cell lung carcinoma

“…The treatment was continued for 31 days. Tumors were measured once or twice a week with microcalipers, and the tumor volume was calculated as length ϫ width ϫ height ϫ 0.5236 (20). At the end of the experiment, mice were anesthetized with methoxyflurane (Metofane; PitmanMoore, Mundelein, IL) and sacrificed by decapitation, and trunk blood was collected.…”

LHRH receptor expression in sarcomas of bone and soft tissue

“…In various studies, analogs of other neurohormones (e.g. GHRH, somatostatin) were shown to inhibit the growth of human experimental osteosarcomas in vivo [10][11][12][13][14] and analogs of LHRH suppressed proliferation of rat chondrosarcomas [15]. In this investigation, we provide immunohistochemical evidence for the presence of receptors for LHRH in sarcomas.…”

Inhibition of growth and reduction in tumorigenicity of UCI-107 ovarian cancer by antagonists of growth hormone-releasing hormone and vasoactive intestinal peptide

“…The treatment was continued for 3 weeks. Tumors were measured twice a week with microcalipers and the tumor volume was calculated as length´width´height´0.5236 (Redding et al 1983). After the last injection, mice were anesthetized with methoxy¯urane (Metofane; Pitman-Moore, Mundelein, Ill., USA) killed by decapitation and trunk blood was collected.…”