Endocrine Abstracts

At birth, requirements for energy in the form of ATP increase as the neonate takes on new postnatal functions such as pulmonary ventilation, thermoregulation and, in some species, locomotion. In many tissues, the morphological and physiological preparations for these neonatal adaptations begin before birth and depend on the natural rises in fetal cortisol and triiodothyronine (T₃) concentrations towards term. Recent studies in sheep have shown that these hormones also have an important role in the prepartum maturation of mitochondria, the major source of ATP. Mitochondrial content, oxidative capacity and abundance of electron transfer system (ETS) complexes of several fetal muscles increase towards term in parallel with the natural surge in fetal cortisol and T₃ concentrations. These prepartum mitochondrial changes can be stimulated prematurely by fetal cortisol infusion earlier in gestation and prevented by abolishing the rise in cortisol towards term by fetal adrenalectomy. Cortisol infusion also increased expression of the genes regulating mitochondrial biogenesis and OXPHOS efficiency while, conversely, adrenalectomy reduced these factors in late gestation. Similarly, prepartum development of muscle mitochondrial function was prevented by fetal thyroidectomy. In addition, prenatal overexposure to cortisol in late gestation altered mitochondrial OXPHOS function in specific muscles in adulthood. Muscle mitochondria are, therefore, responsive to the endocrine environment in utero and can be programmed developmentally with long term consequences for metabolism and ATP production postnatally.