Identification of 3,3'-T2S as a fetal thyroid hormone derivative in maternal urine in sheep.

We measured 3,3'-diiodothyronine sulfate (T2S) in serum and urine (n = 5-6) obtained from euthyroid fetal (94-145 days of gestation, term = 150 days), newborn, and adult sheep and in serum and urine samples from ovine fetuses 13 days after total thyroidectomy conducted between 110 and 113 gestation days (n = 5). Sham-operated twin fetuses served as controls (n = 5). Mean serum T2S concentrations increased progressively from 94 days (74 ng/dl) to 130 days (420 ng/dl), decreasing thereafter to 145 days (197 ng/dl). T2S concentrations in fetal urine peaked at 110 days (117 ng/dl). In hypothyroid fetuses, mean serum and urine T2S were 60 and 53% of control values. To assess the possibility that the T2S in maternal serum/urine is derived from fetal serum 3,5,3'-triiodothyronine (T3), we measured T3, T3 sulfate (T3S), and T2S in fetal serum and in maternal serum and urine after bolus infusion of T3 to the fetus (n = 4). Additionally, T3, T3S, and T2S concentrations were measured in maternal serum and urine after T3 infusion to the maternal ewes (n = 4). Fetal T3 infusion rapidly increased fetal serum T3S and T2S. Maternal serum and urine T3S and T2S concentrations increased, whereas T3 concentrations remained unchanged. Maternal T3 infusion increased in serum and urine T3S and T2S levels, but the levels, relative to T3, were less than values measured after fetal T3 infusion. We conclude that T2S is a normal thyroid hormone metabolite in the ovine fetus and suggest that a major pathway of fetal T2S production is T3 to T3S to T2S.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution and ontogeny of thyrotropin-releasing hormone degrading enzymes in rats.

The distribution and ontogeny of tissue prolyl endopeptidase and pyroglutamyl peptidase I activities were studied in the rat from the 7th day before birth to adulthood. While low levels of prolyl endopeptidase activity were demonstrable in many fetal tissues, activity in brain cortex, hypothalamus, lung, and kidney increased dramatically during the 2 wk after birth, gradually returning to adult levels. In adult rats, levels of tissue prolyl endopeptidase activity were highest in kidney, when compared with the intermediate levels in brain cortex, hypothalamus, and liver. Pyroglutamyl peptidase activity was widely distributed in adult rat tissues with high levels in kidney and liver that exceeded intermediate levels in brain cortex and hypothalamus. Pyroglutamyl peptidase activities in fetal gut, brain, and lung tissue were elevated above adult values. In contrast to the development changes in prolyl endopeptidase activities, pyroglutamyl peptidase activity remained elevated above adult levels only during the first week of life. These results indicate that both prolyl endopeptidase and pyroglutamyl peptidase activities in the rat are developmentally regulated.

Ontogeny of thyroid hormone effect on tissue 5'-monodeiodinase activity in fetal sheep.

Most of the thyroxine (T4) in fetal mammals is deiodinated to the inactive metabolite, reverse triiodothyronine (rT3), via an iodothyronine 5-monodeiodinase in fetal tissues. Maturation of the tissue 5'-monodeiodinase (MDI) enzymes required for conversion of T4 to active triiodothyronine (T3) in the rat, an altricial species, occurs in the postnatal period. To characterize fetal maturation of the enzymes for active T3 production in a precocial species, 5'-MDI activities were measured in liver, kidney, and brain tissue homogenates of ovine fetuses 13 days after total thyroidectomy (Tx) conducted at gestational ages of 99-107 or 129-132 days. Sham-operated twin fetuses served as controls. Hepatic type I 5'-MDI activity was not significantly lowered by Tx in group I but was significantly lower after Tx in group II fetuses. Renal type I 5'-MDI was not affected by Tx in either group. Type II 5'-MDI activity in cerebral cortex was significantly elevated after Tx in both groups I and II fetuses. Tissue sulfhydryl contents were similar in liver, kidney, and cerebral cortex from control and Tx fetuses in group I. These data indicate that hypothyroidism induced early in the third trimester is associated with increased brain type II 5'-MDI activity without significant change in liver or kidney type I 5'-MDI. Late third trimester hypothyroidism is associated with decreased type I 5'-MDI activity in liver homogenates as well as increased type II 5'-MDI activity in brain tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum insulin-like growth factor-I levels in amyotrophic lateral sclerosis.

The serum concentrations of the myotrophic hormone insulin-like growth factor-I (IGF-I) in 23 patients with amyotrophic lateral sclerosis were not significantly different from those found in the sera of 13 control patients. There was no difference in binding of 125I-IGF-I by serum from patients with amyotrophic lateral sclerosis in comparison with that found in the controls. These results indicate that immunoreactive IGF-I concentrations are normal in patients with amyotrophic lateral sclerosis and that such patients do not have significant antibodies binding their endogenous IGF-I.

Epidermal growth factor acts as a corticotropin-releasing factor in chronically catheterized fetal lambs.

Epidermal growth factor (EGF) has been reported to stimulate adrenocorticotropin hormone (ACTH), growth hormone and prolactin secretion from pituitary tissue in vitro, and in large doses evokes ACTH secretion in adult sheep in vivo. In order to assess a possible role for EGF in the pituitary hyperfunction characteristic of the in utero fetus, we measured changes in plasma immunoreactive ACTH concentrations after acute administration of saline, purified mouse EGF or synthetic ovine corticotropin releasing factor (CRF) to chronically catheterized fetal sheep. Both CRF and EGF were associated with increases in plasma immunoreactive ACTH concentrations. Peak values 60 min after 10-micrograms injections of either EGF or CRF increased from baseline ACTH values of 61 +/- 11 pg/ml to 191 +/- 37 and 178 +/- 25 pg/ml, respectively. Dose-response studies indicate that at low doses (less than 20 micrograms) EGF is as potent a stimulus for ACTH release as CRF. EGF infusion was not associated with detectable changes in circulating CRF, catecholamines, arginine vasopressin levels, or plasma growth hormone concentrations. We speculate that EGF may be important in the regulation of pituitary function in the developing mammalian fetus.