THYROTROPIN-RELEASING-HORMONE ACCELERATES FETAL MOUSE LUNG ULTRASTRUCTURAL MATURATION VIA STIMULATION OF EXTRA THYROIDAL PATHWAY

Maternal administration of TSH-releasing hormone (TRH) in the euthyroi d mouse accelerates fetal lung ultrastructural maturation. However, th e mechanism(s) of TRH in fetal lung development remains unclear; it co uld be due to its neuroendocrine and/or neurotransmitter effects. Alth ough the neuroendocrine effect of TRH is mediated via stimulation of t he fetal pituitary-thyroid axis, the neurotransmitter effect is mediat ed via stimulation of fetal autonomic nervous system activity. In the hyt/hyt mouse there is a point mutation in the beta subunit of the TSH receptor in the thyroid gland of the Balb-c mouse. In these mice TSH does not bind to its receptors, leading ultimately to the development of primary hypothyroidism, which is transmitted as an autosomal recess ive trait. A maturational delay in the lung ultrastructure of the hyt/ hyt mouse fetus has been observed. This investigation was undertaken t o study the effect of maternal TRH treatment on lung ultrastructural m aturation in the hyt/hyt mouse fetus. If the effect of TRH is mediated via stimulation of fetal pituitary-thyroid axis, TRH treatment should not enhance lung maturity in the hyt/hyt fetus and vice versa. Adult hyt/hyt mice made euthyroid by triiodothyronine supplementation were m ated to carry hyt/hyt pups. Saline or TRH (0.4 or 0.6 mg/kg/dose) was administered to the mother (i.p.) on d 16 and 17 (b.i.d.) and on d 18 of pregnancy 1 h before killing (term, similar to 20 d). The fetal lun g electron micrographs were subjected to ultrastructural morphometric analysis of the number of lamellar bodies and glycogen/nuclear ratio i n type II cells, and the alveolar/parenchymal ratio by Chalkley point counting with an interactive computerized image analyzer (Optimas, Bio scan). Fetal lungs exposed to the lower dose of TRH (n = 7) showed no significant difference in their ultrastructural maturation when compar ed with saline-treated controls (n = 5). However, fetal lungs exposed to a higher dose of TRH (n = 6) showed increased numbers of lamellar b odies per type II cell, an increase in the alveolar/parenchymal ratio, larger air spaces, thinner alveolar septa, presence of tubular myelin , and increased numbers of air-blood barriers. We conclude that the ef fect of TRH in accelerating fetal mouse lung maturation is at least in part mediated via stimulation of extra thyroidal pathways.