1. In mice and guinea-pigs, the number of glomeruli was counted in kidneys during normal growth and in hypertrophy induced by unilateral nephrectomy. 2. In mice, the number of glomeruli increased sharply during the first 2 weeks in life, and more slowly afterwards. Unilateral nephrectomy, when performed during this period of natural increase, induced the formation of supplementary nephrons in the contralateral kidney. 3. In guinea-pigs, the number of glomeruli was almost complete at birth. No evidence of a supplementary increase in the number of nephrons was found in hypertrophied kidneys following unilateral nephrectomy. 4. These results, together wit previous data obtained in the rat, suggest that the ability to induce new nephrons after unilateral nephrectomy in different species would depend more on the state of kidney maturity at birth than on differences in the renal mechanisms which lead to hypertrophy.

We have developed a pigmented human skin equivalent by inserting a punch biopsy of human infant foreskin as a source of epidermis into a collagen lattice (dermal equivalent). Using a conventional epidermal culture medium and stimulation with UVB irradiation or 8-MOP + UVA treatment, melanocytes were found to grow out from the biopsy with the epidermal sheet. In this newly formed epidermis, melanocytes and keratinocytes were maintained in an architectural relationship similar to that present in vivo and melanocyte outgrowth could be quantitatively evaluated. Consequently, this pigmented human skin equivalent is a useful model for investigating the biology and photobiology of human skin pigmentation.

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Modulation of ␤-adrenoreceptor expression by tumor necrosis factor-␣ (TNF-␣) was investigated in murine 3T3-F442A adipocytes. TNF-␣ treatment of mature adipocytes decreased ␤ 3 -adrenoreceptor mRNA content in a time-and concentration-dependent manner, with a 8.5-fold decrease observed after a 6-h exposure to 300 pM TNF-␣. ␤ 1 -Adrenoreceptor mRNA abundance was slightly decreased by TNF-␣ treatment, while ␤ 2 -adrenoreceptor mRNA levels were potently induced (6-fold increase at 6 h). (؊)-[ 125 I]Iodocyanopindolol saturation and competition binding experiments indicated that TNF-␣ induced a 2-fold decrease in ␤ 3 -adrenoreceptor number, a nonsignificant reduction in ␤ 1 -subtype population, and a ϳ4.5-fold increase in ␤ 2 -adrenoreceptor density. This correlated with a lower EC 50 value measured for epinephrine in stimulating adenylyl cyclase, whereas the EC 50 value for norepinephrine increased. Nuclear run-on assays on isolated nuclei and mRNA stability measurements showed that TNF-␣ increased both ␤ 2 -adrenoreceptor gene transcription and ␤ 2 -adrenoreceptor mRNA half-life, while ␤ 1 -and ␤ 3 -adrenoreceptor gene expression was modulated only at the transcriptional level by the cytokine. These findings demonstrate a differential modulation by TNF-␣ of the three ␤-adrenoreceptor subtypes in adipocytes, which may contribute to metabolic disorders induced by the cytokine in the adipocyte.Tumor necrosis factor-␣ (TNF-␣) 1 is a multifunctional cytokine that was originally identified as a tumoricidal protein (1). Subsequent investigations have shown that TNF-␣ was fundamentally involved in control of the growth, differentiation, and metabolism in several normal cells and tissues.A sum of work has been focused on the role of TNF-␣ in the regulation of adipocyte development and metabolism (1, 2). Thus, TNF-␣ strongly inhibits adipose conversion and even causes a dramatic dedifferentiation of adipocytes in culture (3-6). Moreover, it is also documented that TNF-␣ decreases the synthesis and activity of several proteins essential for lipogenesis and triglyceride accumulation in adipocytes. These include lipoprotein lipase (5, 7-9), acetyl-coenzyme A carboxylase (4, 10, 11), acyl-coenzyme A synthetase (12), stearoyl-coenzyme A desaturase (12), and the insulin-sensitive glucose transporter GLUT4 (13,14).In addition to the above effects on adipogenesis and reduction of de novo fatty acid synthesis, TNF-␣ also depletes triglycerides from adipocytes by directly increasing lipolysis (15-17). So far, the molecular mechanism by which the cytokine potentiates lipolysis remains unclear (17).Through activation of three ␤-AR subtypes, catecholamines exert a key role in the regulation of lipid metabolism in adipocytes. They modulate cAMP-dependent processes such as lipolysis and the genetic control of the lipogenic and thermogenic pathways. As regards the pleiotropic effects of TNF-␣ on several metabolic pathways in adipocytes, and to the key role of the ␤-AR system in lipid mobilization, it is possible that an interplay between TNF...