General Description
White powder. Melting point 121°C. Stable in air. Insoluble in water. A female sex hormone. Low toxicity.
Reactivity Profile
PROGESTERONE(57-83-0) is sensitive to light .
Air & Water Reactions
Insoluble in water.
Hazard
A carcinogen (OSHA).
Health Hazard
ACUTE/CHRONIC HAZARDS: This chemical may be absorbed through the skin.
Fire Hazard
Flash point data for this compound are not available; however, PROGESTERONE is probably combustible.
Chemical Properties
White powder. Melting point 121°C. Stable in air. Insoluble in water. A female sex hormone. Low toxicity.
Definition
ChEBI: A C21-steroid hormone in which a pregnane skeleton carries oxo substituents at positions 3 and 20 and is unsaturated at C(4)-C(5). As a hormone, it is involved in the female menstrual cycle, pregnancy and embryogenesis of humans and ot
er species.
Definition
progesterone: hormone, producedprimarily by the corpus luteumof the ovary but also by theplacenta, that prepares the inner liningof the uterus for implantation ofa fertilized egg cell. If implantationfails, the corpus luteum degeneratesand progesterone production ceasesaccordingly. If implantation occurs,the corpus luteum continues to secreteprogesterone, under the influenceof luteinizing hormone andprolactin, for several months of pregnancy,by which time the placentahas taken over this function. Duringpregnancy, progesterone maintainsthe constitution of the uterus andprevents further release of eggs fromthe ovary. Small amounts of progesteroneare produced by the testes.
Brand name
Crinone (Columbia); Prometrium (Unimed).
Biological Functions
Progesterone is a hormone, produced primarily by the corpus luteum of the ovary but also by the placenta, that prepares the inner lining of the uterus for implantation ofa fertilized egg cell. If implantation fails, the corpus luteum degenerates and progesterone production ceases accordingly. If implantation occurs,the corpus luteum continues to secrete progesterone, under the influence of luteinizing hormone and prolactin, for several months of pregnancy,by which time the placenta has taken over this function. Duringpregnancy, progesterone maintains the constitution of the uterus and prevents further release of eggs from the ovary. Small amounts of progesterone are produced by the testes.
Biological Activity
Endogenous progesterone receptor (PR) agonist (EC 50 = 0.5 nM).
Biochem/physiol Actions
Induces maturation and secretory activity of the uterine endothelium; suppresses ovulation. Progesterone is implicated in the etiology of breast cancer.
Pharmacology
During the second half of the menstrual cycle, progesterone promotes glandular growth in the endometrium, hyperemia of the uterus, thickening of the endometrium in preparation for implantation of a fertilized egg, and reduces the excitability of the uterus during pregnancy, inhibiting its activity and relaxing smooth muscles , allowing the embryo to grow safely. Under the joint action of estrogen, progesterone promotes the development of breast lobules and glands, so that the breasts can fully develop and prepare for lactation. Progesterone closes the cervix, reduces and thickens the mucus, and makes it difficult for sperm to penetrate; in large doses, it inhibits the secretion of pituitary gonadotropin through a negative feedback effect on the hypothalamus, resulting in the inhibition of ovulation. After ovulation, on the basis of the action of progesterone hormone, the endometrium continues to thicken and hyperemia, the glands proliferate and branch, from the proliferative phase to the secretory phase, which is conducive to the implantation and embryonic development of pregnant eggs. Progesterone inhibits uterine contractions and reduces the sensitivity of the uterus to oxytocin, allowing the fetus to grow safely. Progesterone competes against aldosterone, thereby promoting Na and Cl excretion and diuresis. Progesterone can slightly increase body temperature in normal women, so the basal body temperature in the luteal phase of the menstrual cycle is higher than that in the follicular phase.
Side effects
Common side effects of oral Progesterone include: chest pain, chills, cold or flu-like symptoms; cough or hoarseness; fever, and problems with urination. Rare side effects include: clear or bloody discharge; dimpling of the breast skin, lumps in the breast or armpit; persistent crusting or flaking; redness or swelling of the breast; and sores on the breast skin that do not heal. Other side effects that may occur are: abdominal or stomach pain; constipation, difficulty breathing, dizziness, fast, strong, or irregular heartbeat or pulse; headache, measles, indigestion, itching, joint pain, stiffness, or swelling; rash.
Synthesis
Progesterone, pregn-4-en-3,20-dione (28.3.1), is made by oxidizing pregnenolon
with aluminum isopropylate in the presence of cyclohexanone as a proton acceptor
(Oppenauer oxidation). Pregnenolon itself is made by subsequent oxidation
and further cleavage of the side chain of stigmasterin, a sterin of plant origin that is isolated
from soybeans.
Carcinogenicity
Progesterone is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.
Purification Methods
The form crystallises from EtOH with m 127-131o. The -form crystallises from pet ether or aqueous pet ether/aqueous Et2O with m 119-120o or 121o. It also crystallises from Et2O, Me2CO/EtOAc, MeOH, aqueous Et2O, aqueous MeOH, wet pet ether, Et2O/pet ether, pet ether/*C6H6, Et2O/pentane and isopropyl ether. The is at 240nm with log 4.25 (EtOH). [Wintersteiner & Allen J Biol Chem 107 max 321 1934, Beilstein 7 III 3648, 7 IV 2395.]
Toxics Screening Level
The ITSL for progesterone is 0.1 μg/m3 based on an annual averaging time.
References
[1] BIJAN PEDRAM. A Tissue-Selective Nonsteroidal Progesterone Receptor Modulator: 7,9-Difluoro-5-(3-methylcyclohex-2-enyl)-2,2,4-trimethyl-1,2-dihydrochromeno[3,4-f]quinoline[J]. Journal of Medicinal Chemistry, 2008, 51 13: 3696-3699. DOI:
10.1021/jm8004256
