The purpose of this investigation was to study the mechanism of action of a macrophage-derived factor that stimulates steroid production by Leydig cells. This factor increased testosterone production within 30 min, and reached a half-maximal response by 6-8 h. At a maximal dose, it stimulated testosterone production 20-fold at 24 h. Its efficacy was consistently higher than that achieved with a maximal dose of human chorionic gonadotropin (hCG). However, Leydig cells treated with a maximal dose of both the macrophage-derived factor and hCG secreted the same amount of testosterone as when given a maximal dose of only the macrophage-derived factor. The macrophage-derived factor did not require new protein synthesis to stimulate testosterone production, nor did it alter the amount of steroidogenic acute regulatory protein (StAR). While the macrophage-derived factor required an active cholesterol side-chain cleavage complex system, it did not alter the capacity of this enzyme complex. Finally, the macrophage-derived factor was unable to stimulate the production of progesterone by isolated mitochondria. In summary, the macrophage-derived factor is a highly active, acute regulator of steroidogenesis that acts through a high capacity StAR-independent pathway.

The relationship between thyroid hormones and mammalian sleep organization was studied in control, hypothyroid (with and without replacement therapy) and thyroxine-injected adult male rats. The results show an increased number of awakenings during slow wave sleep (SWS) in hypothyroid animals, whereas total sleep time, levels of SWS, paradoxical sleep, and diurnal organization were unaffected by thyroid status. Our findings indicate that adequate levels of thyroid hormone are necessary to sustain extended periods of SWS in the adult rat while hyperthyroid animals show no disruption of sleep organization. A corollary finding is that daily sleep quotas are independent of whole body metabolic rates.

Despite the high incidence and prevalence of otitis media, its pathogenesis is not thoroughly understood. In the last decade, many efforts have been made to provide a better understanding, and abundant information has become available. At the same time the field of immunology has advanced at an extremely rapid pace. We have followed the gradual cellular events in the defense reaction of the middle ear, utilizing eustachian tube obstruction to induce otitis. Seventy-five cats were divided in groups and sacrificed at intervals between one day and six months, and their temporal bones were studied. During an initial phase of inflammation, polymorphonuclears appear at three days in connective tissue; at the same time active fibroblasts synthesize tropocollagen and ground substance while epithelial cells secrete mucus and lysozymes. These cells, together with those involved in the mucociliary transport system and a patent functional eustachian tube, constitute the nonspecific system of defense. The transition cells are the macrophages which appear at one week to interact with T and B cells to produce the specific immune response. Plasma cells appear at two weeks to peak at one month with synthesis of immunoglobulins A, G and M. A secretory immune system is observed. At three and six months, lymphocytes are the predominant cells and occasional accumulations of mononuclears are observed. The reaction involves the entire middle ear, including mucoperiosteum, middle ear muscles and round window membrane. We believe that a better understanding of the middle ear defense system will lead in time to a practical clinical assessment of the immunological status during the evolution of each particular process or disease involving the middle ear, and a more rational approach to the treatment and, hopefully, prevention of chronic ear disease.

Maternal obesity during pregnancy has immediate and long-term detrimental effects on the offspring heart. In this study, we characterized the cardiac and circulatory lipid profiles in fetuses of diet-induced obese pregnant mice and established the changes in lipid abundance and fetal cardiac transcriptomics. We used untargeted and targeted lipidomics and transcriptomics to define changes in the serum and cardiac lipid composition and fatty acid metabolism in male and female fetuses. From these analyses we observed: (1) maternal obesity affects the maternal and fetal serum lipidome distinctly; (2) female heart lipidomes are more sensitive to maternal obesity than male fetuses; (3) changes in lipid supply might contribute to early expression of lipolytic genes in mouse hearts exposed to maternal obesity. These results highlight the existence of sexually dimorphic responses of the fetal heart to the same in utero obesogenic environment and identify lipids species that might mediate programming of cardiovascular health.