Fifty-one focal nodular hyperplasia lesions from 36 patients were examined histologically. Serial sections and three-dimensional models were studied in selected cases. Lesions were multiple in 19% of patients. Thirty-four patients were female. One case had 11 focal nodular hyperplasia lesions and 7 hemangiomata in the liver. Three had astrocytoma and one had anomalous pulmonary venous drainage. Morphometric analysis revealed that the lesions were supplied by an anomalous artery larger than expected for the locale in the liver. This artery branched to form a spider-like structure and was usually not accompanied by a portal vein or duct. Each terminal arterial branch supplied a separate nodule 1 mm in diameter; adjacent nodules coalesced to form the focal nodular hyperplasia lesion. The arterial blood appeared to drain directly into the sinusoids of the nodule. We propose that focal nodular hyperplasia is an hyperplastic response of the hepatic parenchyma to a preexisting arterial spider-like malformation. The frequent coexistence of focal nodular hyperplasia with other vascular and neuroendocrine anomalies suggest that the malformations are developmental in origin. The basic requirement for development of hepatic hyperplasia may be greater blood flow to a region compared to the adjacent parenchyma. This requirement appears to be met in the other forms of nodular transformation of the liver, i.e., nodular regenerative hyperplasia and partial nodular transformation.

The mammalian lung develops from an endodermal tube, derived from an invagination of the primitive foregut, entering the splanchnic mesoderm. This embryonic stage is followed by the pseudoglandular stage of sequential tubular bifurcations. In the subsequent canalicular stage, there is vascularization of the developing lung, which is followed by the saccular stage of acinar development (1). Because lung organogenesis involves cell proliferation, migration, and differentiation, the ontogenic sequence of these events in lung momhonenesis needs to be well coordi---

The glucocorticoid receptor (GR) mediates glucocorticoid stimulation of surfactant production by fetal mammalian lung. In many other tissues, glucocorticoids decrease expression of GR, thereby reducing responsiveness to these hormones. We therefore determined whether there is a similar effect of exogenous glucocorticoids on GR in fetal rat whole lung, and in the principal cell types involved in the stimulation of surfactant, the fibroblasts and the epithelial cells. The ontogeny of GR in late gestation lung differed between the two cell types, with maximal levels occurring in fibroblasts on gestational d 19, and on d 20 in epithelial cells. Administration of dexamethasone (1 mg/kg) to the mother on gestational d 18 or 19 (term = 22 d) increased specific GR binding activity in whole lung 24 h later. Furthermore, in vitro, incubation of cultured fibroblasts of gestational d 20 with 10K7 M cortisol increased GR immunoreactive protein and binding activity in a dose-and time-dependent manner, without affecting cellular levels of GR mRNA. However, identical treatment of d 20 distal airway epithelial cells was followed by decreased GR protein without significant change in cellular GR mRNA. Surfactant protein-A protein levels, taken as assessments of lung maturation, were increased in response to the same treatment. Our findings suggest that hormonal regulation of GR in fetal lung cells occurs at a posttranscriptional level, and is cell-specific. In the context of substantial increases in circulating glucocorticoid concentrations during late gestation, these findings may be of physiologic importance to the biochemical maturation of the antenatal lung. (Pediatr Res 38: [506][507][508][509][510][511][512] 1995) Abbreviations GR, glucocorticoid receptor FBS, fetal bovine serum FPF, fibroblast-pneumocyte factor MEM, minimal essential medium SP-A, surfactant protein-A Glucocorticoids accelerate the onset of mature levels of surfactant synthesis by fetal mammalian lung (1-3) via the classic GR mechanism (1, 2, 4-9). However, in many tissues, glucocorticoids decrease GR expression, thereby decreasing tissue responsiveness to glucocorticoid stimulation. The effect of glucocorticoids on GR in late gestation fetal lung around the time of the onset of augmented surfactant production is incompletely understood.Administration of glucocorticoids decreases GR mRNA (10) and GR protein (1 1) in several adult rat organs, including lung. In various cell lines, glucocorticoids lower GR number by decreasing GR transcription rates without altering affinity for ligand (12,13). However, it is recognized that the response of GR mRNA steady-state levels to glucocorticoid treatment can