Estrogen receptor alpha (ERα) has been implicated in bone’s response to mechanical loading in both males and females. ERα in osteoblast lineage cells is important for determining bone mass, but results depend on animal sex and the cellular stage at which ERα is deleted. We demonstrated previously that when ERα is deleted from mature osteoblasts and osteocytes in mixed background female mice, bone mass and strength are decreased. However, few studies exist examining the skeletal response to loading in bone cell-specific ERαKO mice. Therefore, we crossed ERα floxed (ERαfl/fl) and osteocalcin-Cre (OC-Cre) mice to generate animals lacking ERα in mature osteoblasts and osteocytes (pOC-ERαKO) and littermate controls (LC). At 10 weeks of age the left tibia was loaded in vivo for two weeks. We analyzed bone mass through microCT, bone formation rate by dynamic histomorphometry, bone strength from mechanical testing, and osteoblast and osteoclast activity by serum chemistry and immunohistochemistry. ERα in mature osteoblasts differentially regulated bone mass in males and females. Compared to LC, female pOC-ERαKO mice had decreased cortical and cancellous bone mass, while male pOC-ERαKO mice had equal or greater bone mass than LC. Bone mass results correlated with decreased compressive strength in pOC-ERαKO female L5 vertebrae, and with increased maximum moment in pOC-ERαKO male femora. Female pOC-ERαKO mice responded more to mechanical loading, while the response of pOC-ERαKO male animals was similar to their littermate controls.

This essay considers how scholarly approaches to the development of molecular biology have too often narrowed the historical aperture to genes, overlooking the ways in which other objects and processes contributed to the molecularization of life. From structural and dynamic studies of biomolecules to cellular membranes and organelles to metabolism and nutrition, new work by historians, philosophers, and STS scholars of the life sciences has revitalized older issues, such as the relationship of life to matter, or of physicochemical inquiries to biology. This scholarship points to a novel molecular vista that opens up a pluralist view of molecularizations in the twentieth century and considers their relevance to current science.

This paper concerns the development of a central tenet of modern biochemistry: that cellular metabolism coordinates biological energy supply through the cyclical making and breaking of “energy-rich” phosphate bonds. This interpretation of intermediary metabolism was comprehensively set forth in two review articles published nearly simultaneously (though independently) in early 1941 by German biochemist Fritz Lipmann and Danish biochemist Herman Kalckar. Lipmann and Kalckar first met in the early 1930s in Copenhagen, where they were in frequent contact until 1939, when both left Denmark. Despite the similar claims advanced in Lipmann’s and Kalckar’s reviews, the two men’s presentations differed substantially with respect to their descriptions of “energy-rich” phosphate bonds and their target audiences. In order to explore the circumstances behind these divergences, this paper utilizes a “parallel lives” approach. By analyzing Lipmann’s and Kalckar’s lives in parallel, particular institutional contexts emerge as having been especially significant in shaping their differing interpretations of the power of phosphate bonds. The period that Lipmann spent in muscle researcher Otto Meyerhof’s laboratory (1927–30) conditioned his physiological interpretation of the role of phosphate bonds in cellular energy metabolism. Kalckar’s time at California Institute of Technology (1939–40)—where he was in regular communication with chemists such as Linus Pauling—played the most significant role in his decision to present the power of phosphate bonds from a chemical perspective. Ultimately, an examination of the life stories behind Lipmann’s and Kalckar’s 1941 reviews illuminates how older physiological perspectives were combined with recent advances in theoretical chemistry to explain how energy flows through living organisms.

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