Progesterone (P4) is a steroid hormone and an intermediate of sex steroids produced by all steroidogenic tissues. P4 maintains pregnancy and the secretory condition of the uterine endometrium during the luteal phase, and inhibits the release of gonadotropins.

Discovery

In 1934, progesterone was isolated from the corpus luteum of a pregnant sow’s ovaries. 

Structure 

P4 is a C21 steroid hormone, with a double bond in the A ring and a ketone on carbon 3. 

Properties 

Molecular formula: C21H30O2, Mr 314.46. Two crystalline forms of equal physiological activity exist. Soluble in alcohol, acetone, dioxane, and concentrated H2SO4. Insoluble in water. 

Synthesis and release 

Gene, mRNA, and precursor Progesterone is converted from pregnenolone by the Δ5 ,3β-hydroxysteroid dehydrogenase (3β-HSD) enzyme in the granulosa cells and luteal cells of the ovary, the Leydig cells of the testis, the zona fasciculata and zona glomerulosa of the adrenal gland, and the placenta. The synthesis of P4 varies in different mammalian species. 

Biological functions 

Target cells/tissues and functions PR is expressed specifically in the granulosa cells of preovulatory follicles of the ovary and is required specifically for LH-dependent follicular rupture leading to ovulation.In the luteal phase,progesterone from the luteal cells prevents ovulation and the overproliferation of the endometrial tissue. PR is expressed in the epithelial, stromal, and myometrial cells of the uterus, controlled by estrogen. In the mam mary gland, PR is found in the epithelial and stromal cells. PR is colocalized with ERα in the hypothalamus, medial preoptic area, and arcuate nucleus. Although only estradiol can induce the LH surge, estradiol induces the expression of PRA in the hypothalamus, which can activate kisspeptin neurons in the anteroventral periventricular nucleus.

Use for diagnosis and treatment 

Progesterone has been approved for the treatment of irregular and anovulatory menstrual cycles. Progesterone combined with estrogen is used for hormonal contraception and the prevention of endometrial hyperplasia in postmenopausal hormonal replacement therapy. It is also used without estrogen as a progestin-only contraceptive agent and in alternative treatment for early stages of endometrial cancer (at high dose) in premenopausal women.