Melvin M. Grumbach 1925-2016.

Generations of clinicians have been faced with often striking developmental and acquired hormonal syndromes associated with reproductive, growth, and metabolic phenotypes. These syndromes have included ambiguous genitalia, anomalies of sexual development, intersex forms, accelerated or delayed puberty, gigantism, and short stature. Although clinical phenotypes of these disorders have been well-established, elucidating their pathogenesis remained elusive until the mid1950s. Drawing on his incisive application of novel diagnostic techniques to study neuroendocrine pituitary control,MelGrumbach elucidated criticalmechanisms underlying both normal physiology and pathogenesis of clinical syndromes, ranging from ontogeny of reproductive and growth axis control circuits, to effects of gonadotropin-releasing hormone (GnRH) pulse generation and timing of puberty onset, to control of adrenal androgen production and virilizing syndromes, to male estrogen receptor mutation sequelae. Mel, an icon of investigative endocrinology, passed away onOctober 4, 2016, at the age of 90. Born, raised, educated, and trained as a physician, pediatrician, and endocrinologist in New York, Mel spent the latter 50 years of his stellar career at the University of California, San Francisco (UCSF), where he founded much of the knowledge base for our understanding of endocrine control of human reproductive development and growth. At the onset of his remarkable career of endocrine discovery in the mid-20th century, structural identification of peptide hormones and regulation of pituitary function were yet obscure. Hypothalamic hormonal control of normal and diseased human pituitary function was not yet characterized, assays formeasuring hormones in the clinic were not sophisticated and were technically laborious, and mechanisms underlying hormone action mediated by receptor signaling were unknown (1). By the end of Mel’s career, he had both intimately witnessed the explosion of hormone discovery and also actively participated in the unprecedented knowledge spurt unraveling genetic and acquired mechanisms for a myriad of endocrinopathies, primarily but not limited to children. Mel created an enduring legacy and comprehensive standard body of scholarship for reproductive development, meticulously describingmechanisms underlying normal humangrowth and sexual development. Graduating in 1948 from Columbia University, Mel embarked on a remarkable career trajectory in investigative pediatrics, intrigued by the then embryonic specialty of endocrinology. After fellowship training with the legendary Lawson Wilkins at The Johns Hopkins University in Baltimore, Mel was appointed founding director of Pediatric Endocrinology at Babies Hospital in 1955. In 1965, Mel moved to UCSF to chair the Department of Pediatrics, his home for 50 years. He propelled the department to the highest rankings and in 2010 was Melvin M. Grumbach. Image courtesy of Susan Merrell (University of California, San Francisco).