Partially redundant functions of SRC-1 and TIF2 in postnatal survival and male reproduction

Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition

“…The lungs of these fetuses manifested alveolar collapse (29), possibly due to impaired surfactant glycerophospholipid synthesis. To determine the enzyme(s) in the surfactant glycerophospholipid pathway that may be affected by the combined deficiency in SRC-1 and SRC-2, we analyzed expression of those enzymes catalyzing the key metabolic reactions.…”

“…Fetal plasma glucocorticoids increase exponentially during late gestation (14) and are thought to serve a role in maturation of the fetal lungs (63)(64)(65)(66)(67)(68). Neonatal mice in which SRC-1 and SRC-2 were both knocked out were reported to have diffuse lung atelectasis and died at birth of apparent respiratory distress (29). Importantly, we observed that the decreased expression of LPCAT1 in lungs of SRC-1/-2-deficient fetuses was associated with profoundly reduced secretion of DPPC into AF.…”

“…Mice in which SRC-1 and SRC-2 have both been knocked out die at birth of respiratory distress (29). To investigate the mechanisms whereby deficiency of SRC-1 and SRC-2 cause decreased production of pulmonary surfactant components, we crossed SRC-1/-2 dhet mice.…”

“…Male SRC-2 -/-mice are infertile due to defects in spermatogenesis (27), while female SRC-2 -/-mice display placental hypoplasia and hypofertility (28). In light of our previous findings that SRC-1 and SRC-2 serve roles in the regulation of SP-A gene expression, we were intrigued by the finding that mice lacking both SRC-1 and SRC-2 (SRC-1 -/-SRC-2 -/-mice, herein referred to as SRC-1/-2 dKO mice) died at birth of respiratory distress (29), suggesting a deficiency of pulmonary surfactant production.…”

Disruption of the SRC-1 gene in mice suppresses breast cancer metastasis without affecting primary tumor formation

“…In addition to nuclear receptors, members of the SRC family also interact with and coactivate other transcription factors such as Ets-2, PEA3, and E2F1 (4)(5)(6)(7)(8)(9)(10)(11). Studies using mutant mouse models have shown that the members of the SRC family have both unique and partially redundant biological functions in development, somatic growth, steroid hormone response, metabolism, reproduction, cardiovascular system, and inflammatory response (3,(12)(13)(14)(15)(16)(17)(18)(19)(20).…”