An Endocrine Society Thematic Issue: Summer Retrospective 2019

In 1978, work published in Endocrinology by Mueller and Kim demonstrated that various alkylphenols could bind to the estradiol receptor.² Further research identified such molecules acting as estrogens. In this 1994 study, the effects of several alkylphenolic compounds were tested on avian and mammalian cells, thus starting the elucidation of the mechanism behind their estrogenic effects. This highly influential work has been cited 960 times and influenced policy documents on environmental endocrine-disrupting chemicals:

“…the widespread use of the chemicals and the persistence of their degradation products in the environment coupled with the concern about inadvertent exposure of wildlife and humans to “estrogens” raises considerable disquiet.”

The gamma isoform of peroxisome proliferator activated receptor (PPARγ) was isolated and identified in 1993 but was not characterized until this Endocrinology study in 1994.^{3, 4} The authors demonstrated that PPARγ was rapidly and significantly induced by peroxisome proliferators and that its expression was restricted to specific tissues, with substantial expression in adipose tissue. These initial findings suggested a role for PPARγ in regulating adipocyte differentiation and regulation. It has since been implicated in the pathology of many disorders, including diabetes, obesity, and cancer. This publication has received 534 citations since 1994.

“Together, the highly regulated and dramatically enriched expression of PPARγ in adipose tissue along with adipogenic effect of PPAR activators strongly suggests that PPARy plays an important role in adipocyte differentiation and maintenance.”

The identification of a male odor — later described and known as a “pheromonal effect” — that regulates the onset of sexual maturity in mice was first described in this study.

“The purpose of the experiment described in this report is to determine whether sexual maturation can be accelerated by increasing general physical activity, whether physical contact between the sexes is required, and whether male odor alone can account for the observed hastening of female sexual maturity.”

This publication describes the development of highly sensitive and specific immunoassays for the determination of luteinizing hormone levels in serum from cattle or sheep. This publication has been cited 1,167 times and the methods described are still used in endocrinology research today.

This was an early in vivo study examining the levels of estrogen in the blood of rats, determining the changes in estrogen secretion during the estrous cycle and pregnancy. This highly influential research (584 citations) significantly impacted the field’s knowledge of estrogen signaling and is still being read and cited today.

During the late 1920 and early 1930s, Allen and Corner discovered progesterone while working in their embryology laboratory. They first maintained pregnancy in rabbits with corpus luteum extracts. Allen wrote an article titled “My Life with Progesterone” in which he described the day that progesterone was successfully isolated: “…the isolation of the hormone from the waxy material obtained by high-vacuum distillation was a laborious and exasperating experience. However, the month of May 1933 was a glorious month. On May 5, I had the crystalline corpus luteum hormone. On May 18, my daughter, Lucille, was born. My friends gave me double congratulations and I was sitting on top of the world.”⁵

Csapa and Wiest worked to define the role of progesterone in the establishment and maintenance of pregnancy and this 1969 Endocrinology study “…adds further support to the primacy of ovarian hormone supply… and implicates the placenta as a supplementary source. In addition, it provides evidence that pregnancy maintenance is correlated with the concentration of progesterone in the uterus.”

DHEA (dehydroepiandrosterone) is a hormone that has garnered attention for its potential anti-aging effects. 25 years ago, this JCEM study tested the hypothesis that DHEA may have beneficial effects on neuroendocrine-metabolic function in humans and may affect the aging process: “Our results support the hypothesis that DHEA may indeed have a biological function in man…” The results from this study stimulated many studies into IGF-1 signaling and hormone treatments for aging and other disorders. It continues to stimulate discovery (563 citations and 8 patents).

“This study, using a battery of biochemical markers of bone turnover, clearly demonstrates that bone remodeling is increased in late-PMP (post-menopausal) osteoporotic women.”

“Many investigations have been made to elucidate the mechanism of sleep, which is vitally important for the maintenance of life.” This early paper investigated the endocrine aspects of sleep and demonstrated an important role for growth hormone. The study focused on the neuroendocrine aspects of sleep and was fundamental for many follow-up studies. It has been cited 156 times and is considered a seminal paper in the study of sleep and hormones.

Want to know how one of the immunoassays used to measure angiotensin I and its application for the determination of renin activity were developed? This paper describes the development of the assay and is cited in hundreds of Material & Methods sections of papers requiring the accurate measurement of renin content (>1900 citations, 19 patents).

“One of the most pressing needs in the general field of hormone assay is the development of techniques of sufficient sensitivity…to study acute physiological changes.” This JCEM paper describes the invention of solid-phase radioimmunoassay of estradiol-17β. Immunoassays for measuring estradiol have been used since this paper was published and excitingly, assays continue to evolve to improve detection limits and specificity. This method has been used in countless analyses of estradiol, has been cited over 700 times, and was essential for the widespread use of the steroid immunoassay.