Influence of Pre- and Postnatal Thiouracil Administration on Pituitary Growth Hormone Content in Mice

We examined the influence of thiouraeil-induecd hypothyroidism imposed at various stages of development upon pituitary growth hormone (OH) concentration. Balb/e-derived mice were mated and fed thionracil, 0.25% in Purina Lab Chow, from the first day of pregnancy until 25 days postpartum, or for shorter periods of time (last % of pregnancy and postpartum, last j/$ of pregnancy and postpartum, or postpartum only). Using disc gel eleetrophoresis, pituitary Gil concentration of 25 day old pups exposed to thiouracil was compared with that of unexposed animals. Concentration of pituitary GH was depressed significantly in animals whose mothers were first given thiouracil at the initiation of pregnancy or \% of the way through pregnancy. Young of mothers first given thiouracil % of the way through gestation or on the first day postpartum did not have significantly lower pituitary GH concentrations than controls. The factor determining the presence or absence of thiouracil-induced depression of pituitary GH concentration may be the initiation of fetal thyroid function that occurs between days 15-17, approximately % of the way through gestation. OHIO J. SCI. 79(6): 267, 1979 Hypothyroidism induced around the time of birth has long been known to retard skeletal development and growth in rats (Salmon 1938). Mice born of euthyroid mothers were reported to grow faster than those of thyroidectomized dams (Davenport and Swingle 1927). More recent studies have suggested that growth is depressed because of reduced synthesis or secretion of growth hormone (GH) induced by the hypothyroid condition. For example, Peake et al (1973), using radioimmunoassay, and Wilkins et al (1974) using disc gel column eleetrophoresis have shown altered pituitary GH concentration in pituitaries of rats made hypothyroid as young adults. Furthermore, pituitaries of rats thyroidectomized at birth are virtually devoid of GH at 25 days of age (Geel and Timiras 1970). The length of time necessary for hypothyroidism to alter GH status has not been extensively studied. Hamburgh (196S) suggested that withholding thyManuscript received 16 August 1978 and in revised form 19 February 1979 (#78-47). roid hormone from developing rats in utero does not appreciably alter maturation of the nervous and skeletal systems. Our study was carried out to determine the importance of thyroid status during development as a factor in establishing postnatal pituitary growth hormone concentration. Hypothyroidism was induced by exposing mice to thiouracil, a drug that prevents thyroid hormone formation, during a portion of gestation and postnatally. MATERIALS AND METHODS Female Balb/c-derived mice were mated to males of the same strain. First day of pregnancy was determined by presence of a vaginal plug. Pregnant females were isolated and assigned to one of the following feeding schedules (see fig. 1): (A) Thiouracil diet from the first day of pregnancy to 25 days postpartum (46 days of thiouracil exposure). (B) Control diet during the first ]/A of pregnancy, and thiouracil diet during the last % of pregnancy to 25 days postpartum (39 days). (C) Control diet for the first % of pregnancy, and thiouracil diet during the last /i of pregnancy to 25 days postpartum (32 days).