The history of natural progesterone, the never-ending story.

The term progesterone should only be used for the natural hormone produced by the ovaries or included in a registered drug. The modern history of progesterone begins with the first book-length description of the female reproductive system including the corpus luteum and later with the Nobel Prize winner, Adolf Butenandt who took a crucial step when he succeeded in converting pregnanediol into a chemically pure form of progesterone, the corpus luteum hormone. The deficient production of progesterone was shown first to be the cause of the luteal-phase deficiency responsible for infertility and early pregnancy loss due to inadequate secretory transformation of the endometrium. Later, progesterone was confirmed to be the best and safest method of providing luteal-phase support in assisted reproductive technology. Progesterone provides adequate endometrial protection and is suggested to be the optimal progestagen in menopausal hormone therapy in terms of cardiovascular effects, venous thromboembolism, probably stroke and even breast cancer risk. Neuroprotective effects of progesterone have also been demonstrated in several of experimental models including cerebral ischemic stroke and Alzheimer's disease. Vaginal progesterone was shown to decrease the risk of preterm birth in women with a mid-trimester sonographic short cervix and to improve perinatal outcomes in singleton and twin gestations.

Uncommon trajectories: steroid hormones, Mexican peasants, and the search for a wild yam.

This article analyzes how evolving pharmaceutical technology, chemical advances, and world politics created the need for an abundant and cheap supply of steroids, and how decisions made in faraway laboratories ultimately determined that a Mexican yam, barbasco, was the best possible raw material. Following this discovery, this article explores how barbasco's exploitation impacted on the Mexican countryside and specifically the men and women hired to gather wild yams. In analyzing, for example, the peasant organizations that emerged, the use of chemical terms by barely literate peasants, and the Mexican government's political strategy to control rural unrest by controlling barbasco production one begins to understand the unexpected consequences of the global search for medicinal plants. In this particular case, the merging of science and peasant life reshuffled social hierarchies in the countryside, granted monetary value to an erstwhile 'weed', and gave a novel reinterpretation to laboratory knowledge and its (social) uses.

Hormones, mammary growth, and lactation: a 41-year perspective.

When I was a beginning graduate student 41 yr ago it had been established that estrogen caused mammary duct growth; a combination of estrogen and progesterone was required for lobule-alveolar development of the mammary glands; and prolactin and growth hormone were essential for mammary growth. In laboratory species exogenous prolactin, glucocorticoids, and estrogen would initiate secretion of milk provided the mammary glands had a well-developed lobule-alveolar system. It was not known with certainty that progesterone inhibited the process. For some species, prolactin and thyroxine had been shown to stimulate lactation, while glucocorticoids suppressed lactation. Definitive roles for growth hormone and insulin during lactation had not been established. Studies of hormonal control of mammary growth and function in cattle were few. In vitro methods to study hormonal regulation of the mammary glands were in their infancy. Quantitative measures of changes in mammary cell numbers and specific components of milk in response to hormones were rare. The concepts for quantification of hormone concentrations, hormone receptors, growth factors, and binding proteins in blood; hormonal regulation of nutrient partitioning; and hormonally induced mechanisms of action within mammary cells were waiting to be discovered. And eventually they were. However, lest we become too enamored with our current understanding of the hormones that control mammary growth and lactation, it remains a fact that the greatest physiological stimulus for milk yield is pregnancy, not some cocktail of exogenous hormones, growth factors, receptor agonists/antagonists, or gene therapies. Viva la mom!

Ludwig Fraenkel: 'spiritus rector' of the early progesterone research.

The search for the corpus luteum hormone progesterone took more than three decades and the efforts of many scientists all over Europe and the USA. In 1934, after a dramatic neck-and-neck scientific race, four research groups independently from each other reported on the successful isolation of the pure substance. Two of the groups were from the then-German cities of Breslau and Danzig, the others were from the USA and Switzerland. Possibly, the Breslau group had already had the purified hormone as early as 1933. At that time, gynecologist Ludwig Fraenkel (1870-1951) had been their 'spiritus rector' for more than three decades. It was Fraenkel himself who at the beginning of the century, in examining a hypothesis of the anatomist Gustav Jacob Born (1851-1900), had provided experimental proof for an endocrine function of the corpus luteum. Later on, Fraenkel enlisted the help of chemist Karl Heinrich Slotta (1895-1987) in the purification of the hormone. This took place after important requirements for the isolation and for the semiquantitative determination of the hormone (e.g. Corner-Allen test) had been established elsewhere. Also belonging to the Breslau research group were Erich Fels (1897-1981) and Heinrich Ruschig (born in 1906). Fels was an assistant to Fraenkel, Ruschig a PhD candidate directed by Slotta. Shortly after the group had succeeded in purifying progesterone, the Breslau group was broken apart by the National Socialist's racial policies: Fraenkel, Fels and Slotta were forced into emigration.

[Ludwig Fraenkel, corpus luteum and discovery of progesterone]. / Ludwig Fraenkel, das Corpus luteum und der Weg zum Progesteron.

In 1934, after a dramatic neck-and-neck scientific race, four research groups independently from each other reported on the successful purification of progesterone. Two of the groups were from the then-German cities of Breslau and Danzig, the others were from the USA and Switzerland. Possibly, the Breslau group had already had the purified hormone as early as 1933. At that time, gynecologist Ludwig Fraenkel (1870-1951) had been their "spiritus rector" for more than three decades. It was Fraenkel himself who at the beginning of the century, in examining a hypothesis of the anatomist Gustav Jacob Born (1851-1900), had provided experimental proof for an endocrine function of the corpus luteum. Later on, Fraenkel enlisted the help of chemist Karl Heinrich Slotta (1895-1987) in the purification of the hormone. This took place after important requirements for the isolation and for the semiquantitative determination of the hormone (e.g. the Corner-Allen-Test) had been established elsewhere. Also belonging to the Breslau research group were Erich Fels (1897-1981) and Heinrich Ruschig (born in 1906). Fels was an assistant to Fraenkel, Ruschig a PhD-candidate directed by Slotta. Shortly after the group had succeeded in purifying Progesterone the Breslau group was broken apart by the National Socialists' racial policies: Fraenkel, Fels and Slotta were forced into emigration.