Synergistic Action of Triiodothyronine and Hydrocortisone on Epinephrine-Induced Reabsorption of Fetal Lung Liquid

Abstract

ABSTRACT. The influence of triiodothyronine and hydro-However, precocious exposure of the fetus to T3 at an early cortisone on maturation of the response to epinephrine that gestation did not significantly advance the time of appearance of leads to reabsorption of lung liquid was investigated in nine this reabsorptive capacity, from which it could be concluded that chronically catheterized fetal sheep. Experiments were some other factor must play a role in determining its maturation performed on thyroidectomized fetal sheep at 116-120 d during gestation. Steroid hormones, alone or in combination gestation, well before the reabsorptive response to epi-with thyroid hormones, are known to be important in determinnephrine is normally seen. After i.v. administration of ing the maturation of structural aspects of the lung and its either triiodothyronine (60 ~g / d ) or hydrocortisone (10 mg/ surfactant system in the fetus (8, 9). Our experiments were d) for 3 d (three fetuses in each case), all fetuses continued undertaken to examine the influence of hydrocortisone alone to secrete lung liquid during exposure to epinephrine (se-and in combination with T3 on the maturation of the reabsorpcretion rate = 5.9 f 3.2 mL/h in triiodothyronine-treated tive response. Fetal sheep were studied at 116-120 d, which is a and 4.4 2 1.9 mL/h in hydrocortisone-treated fetuses). gestation well before that at which the reabsorptive response to However, when the two hormones were administered to-epinephrine normally appears. gether in the same doses to three fetuses, a striking reabsorptive response to epinephrine was seen (absorption rate MATERIALS AND METHODS= -12.3 f 3.6 mL/h), similar to that observed in the mature fetus. Induction of this capacity to reabsorb lung Experimental preparation. The surgical preparation of chronliquid may be of importance in the management of respi-ically-catheterized fetal sheep to allow for repeated measurement ratory problems of the newborn infant. (Pediatr Res 27: of lung liquid secretion or absorption rate was identical to that 588-591,1990) described in detail by Walters and Olver (3). Nine dated, pregnant ewes were operated on at 1 12-1 15 d gestation under general Abbreviations anesthesia induced by thiopentone and maintained with fluothane. Fetal thyroidectomy was carried out and wide bore (inner T3, triiodothyronine diameter, 2.6 mm) catheters placed into each end of the incised T4, thyroxine fetal trachea, finer gauge catheters were inserted into the carotid TRH, thyrotropin-releasing hormone artery and jugular vein. The catheters were brought out through the uterus and flank of the ewe and the tracheal catheters joined to form an external loop that allowed uninterrupted flow of lung liquid from the fetal lung to the larynx between experiments. After surgery, antibiotics were given for the first 48 h to the ewe The secretion of lung liquid by the pulmonary epithelium (streptomycin 500 mg intramuscularly, benzyl penicillin 300 mg maintains expansion and promotes development of the fetal lung int...

Invited Review: Clearance of lung liquid during the perinatal period

“…Neither T 3 nor hydrocortisone given individually was capable of advancing maturation of the epinephrine response in normal fetuses with intact thyroid glands, but a powerful synergistic effect was observed when T 3 and hydrocortisone were given concurrently (8). In thyroidectomized fetal lambs, the response to epinephrine was detectable within 2 h of the start of infusion of the hormone combination, and recovery of function, which could be blocked by the protein synthesis inhibitor cyclohexamide, was lost within 24-48 h of cessation of hormone administration (13).…”

Aquaporin-1 water channel protein in lung: ontogeny, steroid-induced expression, and distribution in rat.

“…Corticosteroid induction of AQP1 in lung is consistent with other observations suggesting hormonal modulation of lung development. Triiodothyronine and cortisol accelerate lung water clearance in thyroidectomized sheep (35,36) and accelerate expression of sodium channels in fetal rat lung (30). Surfactant proteins, integral to the function and homeostasis of the surfactant system, have a very similar ontogeny in lung to AQP1 (37).…”

Hormonal modulation of Na+ transport in rat fetal distal lung epithelial cells

“…Although this effect was reversed by infusion of T 3 (Barker et al 1990b), delivering T 3 to immature fetuses did not cause precocious maturation of the response unless given in conjunction with a glucocorticoid (Barker et al 1990a). The functional maturation of the lung in utero thus seems to be dependent upon simultaneous exposure to thyroid and glucocorticoid hormones (Gross et al 1984;Barker et al 1990a) and it is now clear that the levels of both hormone classes rise sharply during the perinatal period (for example see Polk, 1995;Baines et al 2000). These data, when taken together with the present results, suggest that exposure to dexamethasone and T 3 may underlie the increasing sensitivity to b-adrenoceptor agonists that develops during the final stages of gestation (Walters & Olver, 1978;Brown et al 1983).…”

“…In fetal lambs, as well as blocking the maturation of the response to adrenaline, thyroidectomy prevents the developmental regulation of the response to a cell-permeant cAMP analogue, suggesting that the permissive effects of thyroid and glucocorticoid hormones are mediated at a site downstream of b-adrenoceptor-mediated cAMP formation (Barker et al 1988(Barker et al , 1990a). The present study tested this hypothesis by exploring the effects of isoprenaline upon the conductive properties of the apical plasma membrane.…”

“…As thyroid and glucocorticoid hormones influence the development of the surfactant-secreting mechanism and the functional maturation of pulmonary ion transport processes (for example see Gross et al 1984;Barker et al 1988Barker et al , 1990aRenard et al 1995;Tchepichev et al 1995;Barquin et al 1997;Grubb & Boucher, 1998;Norlin et al 1999;Otulakowski et al 1999), we first explored the effects of maintaining FDLE cells in medium supplemented with either T 3 or dexamethasone. Data from unstimulated cells showed that these hormones increased basal I SC , indicating that they can stimulate Na + transport.…”