Progesterone is the oldest hormone known to man, followed by Vitamin D3 (cholecaliferol). Vitamin D3 is also categorized as a vitamin, it gets converted by the liver to calcidiol, which in turn is converted by the kidneys and other tissues to calcitriol which is a potent steroid hormone.

The history of progesterone covers approximately a 500 million years, which is considered to be its time frame of existence. In 2010 the discovery of progesterone in the molecules of the walnut tree would suggest that its origin has been pushed back even further. Researchers believe that the hormone might be an ancient bio-regulator that evolved billions of years ago, even long before plants and animals appeared. The new discovery may change scientific understanding of the evolution and function of progesterone in living things.

Progesterone and Vitamin D3 are both made from cholesterol:

  • Progesterone in various organs and cells
  • Vitamin D3 by the action of UVB sunlight as it hits the cholesterol which covers our bare skin

In 2009 researchers found that a lack of Vitamin D3 reduced the benefits of progesterone.

They both:

  • regulate gene expression
  • have a positive fundamental effect on cell differentiation and growth with anti-oxidative and autoimmune anti-inflammatory mechanisms
  • positively affect the nervous system by stimulating neurotrophic factors, quenching oxidative hyperactivity and regulating autoimmune responses. Could it be that these two hormones evolved from the same source but split millions of years ago?

Facts about Progesterone

  • Molecular Formula C21H30O2 (Carbon 21, Hydrogen 30, Oxygen 2)
  • Molecular weight 314.46
  • Synonym 4-pregnene-3,20-dione
  • Melting point 126 C (259 F)
  • Bioavailability prolonged absorption
  • Protein binding 96%-99%
  • Metabolism hepatic to pregnanediols and pregnenolone
  • Terminal half-life 13.18 1.3
  • Excretion renal

Facts about Plant Sterols

Phytosterols are molecularly similar to cholesterol found in animals. Cholesterol is the starting point for the steroid hormones made naturally in animals, including humans.

The following plants and more, contain Phytosterols:

  • soy bean
  • dioscorea ~ species of yams
  • fenugreek
  • sisal
  • calabar bean
  • various lilies
  • yucca
  • some solanum species
  • maize

Some of these are:

  • stigmasterol
  • diosgenin
  • sitosterol
  • campesterol
  • hecogenin
  • sarsasapogenin
  • salasodine

The above sterols have a similar molecular structure to cholesterol which are used as starting points for synthesising progesterone. Progesterone is further synthesised into testosterone, estrogen, cortisone etc.

Concerns about Soy

Many people are confused about how progesterone is made and where it comes from. The confusion arises because many websites and blogs provide misinformation, some say that it is made from yam, while others say that it is made from soy.

As mentioned above, progesterone is made from various plant sterols, all plants have sterols which are often called phytosterols. Progesterone is made from various plant sterols, all plants have sterols which are often called phytosterols. Plants such as the soy bean, Dioscorea species of yams, fenugreek, sisal, Calabar bean, some lilies, yucca, some solanum species, maize and many more contain phytosterols. Some of which are stigmasterol, diosgenin, beta-sitosterol, campesterol, hecogenin, sarsasapogenin, solasodine. As these plant sterols have a similar molecular structure to cholesterol, they are used as starting points for the synthesis of progesterone. So the synthesis ends with a progesterone molecule, or molecules. It is only progesterone and can only be progesterone. If it was contaminated with anything else, be it yam, soy or any other plant, it would not be legal to call it progesterone. The bottom line is, it does not matter what plant is used for synthesising progesterone, the end result is progesterone, nothing more and nothing less.

Progesterone in modern history started with its discovery and isolation by Professor Willard Allen who first trained as an organic chemist. He then went on to study medicine. While working in Professor George Corners' embryology lab, the two discovered a substance in the corpus luteum that sustained pregnancy.

On the 23 September 1929, Willard Allen Ph.D published the first paper on extracting progesterone from the corpus luteum.

"In previous papers of the present series we have described the preparation and effects of extracts of the corpus luteum. These extracts, when injected into recently spayed female rabbits, regularly bring about a special histological and physiological state of the endometrium, characteristic of early pregnancy, and known by previous experimentation to be due to the corpus luteum. We have as yet proposed no name for this hormone of the corpus luteum, referring to it only as a hormone which induces the above-described characteristic effects in the rabbit. In so far as we are acquainted with its physiological behavior, its chief action lies in its ability, by alteration of the endometrium, to aid gestation in the castrated rabbit; and for this reason we wish to propose for it the name progestin, i.e., a substance which favors gestation."

It was only in 1933 that the pure hormone was isolated and later named progesterone. An article called “Recollections of my Life with Progesterone by Willard Allen recounted the discovery and isolation in 1974.

Progesterone, an unfortunate name in that it is now known as a female hormone, but also a sex hormone. Because of this, many other roles have been overlooked sadly.

Progesterone is NOT a sex hormone, it plays no part in the secondary sexual characteristics which develop at puberty, which are governed by estrogen in females and testosterone in males. There are no differences between men and women other than the luteal phase. Progesterone is secreted primarily by the ovaries in females and the testes in males. Small amounts are produced by the adrenal glands, the brain and the glial cells. It is the precursor to the sex hormones estrogen and testosterone, as well as the adrenal hormones, cortisol and aldosterone.

In 1929 Adolf Butenandt Ph.D isolated estrone, one of a group of steroids known collectively as estrogen. Edward Doisy, discovered estrone. In 1931 Adolf Butenandt isolated aldosterone at the same time confirming the existence of yet another estrogen called estriol. This had been discovered earlier by G F Merrian but was never confirmed.

In 1933, for the first time, the similarity between the molecular structures of androsterone and cholesterol were found. In 1934 Adolf Butenandt isolated a small sample of progesterone from the corpus luteum, corresponding with Willard Allen about their independent discovery.

In 1935 Ernst Laqueur isolated testosterone from the testes. Shortly after, both Adolf Butenandt and Leopold Ruzicka synthesised testosterone from androsterone. They were both awarded the Nobel Prize for Chemistry in 1939.

Around the same time, Percy Julian Ph.D extracted stigmasterol from the West African Calabar bean or Physostigma Venenosum. He was an amazing chemist who was awarded 130 patents and many honorary degrees. He is best known for his work in the industrial synthesis of human steroids from plant sterols. His work later lead to the production of cortisone. He isolated stigmasterol from soybean oil in 1939. By 1940 he was able to produce the hormone progesterone in bulk.

In 1936 Russell Market isolated the steroid pregnanediol from an extract of pregnant mares urine. He converted this to progesterone in 1937. In 1938 he found the sterol sarsasapogenin from the sarsaparilla plant, could be converted into progesterone using a technique which has since become known as the Market Degradation. However, sarsaparilla was expensive so he continued searching and found the sterol diosgenin in 1941. The diosgenin in the Dioscorea species of a yam growing wild in Mexico which could also be converted into progesterone. Sadly no pharmaceutical company was interested in his discovery. So, in 1943 he used a friend’s lab and converted the diosgenin into three kilograms of progesterone. In 1944 he formed Syntex in Mexico City with two partners, a company which competed with Percy Julian’s soybean progesterone.

Because of the low cost of Russell Market’s progesterone, it later became the preferred precursor to cortisone and by 1951 Syntex had developed the first oral contraceptive from progesterone.

 

References

Occurrence of Progesterone and Related Animal Steroids in Two Higher Plants

Vitamin D deficiency reduces the benefits of progesterone treatment after brain injury in aged rats

Progesterone with Vitamin D affords better Neuroprotection against Excitotoxicity in Cultured Cortical Neurons than Progesterone alone

Combination treatment with progesterone and vitamin D hormone may be more effective than monotherapy for nervous system injury and disease

Sterols. XXXII. Oxidation of Stigmasterol by Selenium Oxide

Physiology of the Corpus Luteum by Willard Allen

Crystalline Progestin

Recollections of my Life with Progesterone

Willard Myron Allen

Adolf Butenandt

Percy Julian The Forgotten Genius

Percy Lavon Julian

Russell Earl Marker