Background
Progesterone (P4), chemical name: pregnane-4-ene-3,20-dione, is an endogenous steroid and progestin (a type of sex hormone) that participates in the menstrual cycle, pregnancy and embryogenesis in humans and other species. It is the main progestin in the body, and most of it is secreted by the luteal cells of the corpus luteum of the female ovary. Progesterone belongs to a class of hormones called progestogens, and together with estrogen, it participates in the regulation of the hypothalamus-pituitary-ovarian axis. When the ovary ovulates in the middle of the menstrual period, the follicle that releases the egg will form a corpus luteum, thereby secreting progesterone. Progesterone causes the endometrium to transform from a proliferative phase to a secretory phase, maintaining its thickness until the onset of menstruation, when the corpus luteum shrinks and the progesterone concentration in the blood drops sharply, causing the endometrium to shed and form menstruation. Progesterone promotes the growth of glands in the uterine mucosa and thickens the endometrium in the late menstrual period, providing favorable conditions for the implantation of the fertilized egg (fertilized egg) and the nutrition of the early embryo and maintaining pregnancy; if the progesterone level is low, menstruation will be delayed. For non-pregnant women, progesterone is only secreted in large quantities by the corpus luteum of the ovary in the second half of each menstrual cycle. It is also secreted by the brain, liver and adrenal glands. During pregnancy (starting in the third month), the placenta can also secrete large quantities. Progesterone is an intermediate in the synthesis of most steroid hormones, including a key metabolic intermediate of sex hormones and corticosteroids, and plays an important role as a neurosteroid in brain function.
Figure 1. Molecular structure of progesterone.
Studies have found that in mammals, progesterone is synthesized from pregnenolone, which is converted from cholesterol. Cholesterol undergoes two oxidations in the body to become 20,22-dihydroxycholesterol. This vicinal diol compound is further oxidized to break the side chain of C-22 to produce pregnenolone. After that, there are two main steps from pregnenolone to progesterone: 1. The 3-hydroxyl group of pregnenolone is oxidized to a keto group; 2. The double bond is transferred from C-5 to C-4. The physiological functions of progesterone are mainly manifested in the following aspects: Endometrium: progesterone mainly promotes the secretion changes of the endometrium to prepare for the implantation of the fertilized egg; after ovulation, progesterone also causes the cervical mucus to thicken, which is not conducive to sperm penetration. Fallopian tube: progesterone also promotes the secretion changes of the fallopian tube mucosal lining, which is related to the nutrition required for the fertilized egg to pass through the fallopian tube a few days before implantation in the uterus. Breast: Under the combined action of estrogen, progesterone promotes the development of breast lobules and breast alveoli. However, progesterone alone will not cause the breast to secrete milk, and a large amount of prolactin is required to produce milk. Progesterone also causes an increase in basal body temperature. Immunity: During implantation and pregnancy, progesterone seems to reduce the mother's immune response in order to accept pregnancy; it helps to suppress the immune response to fetal antigens, thereby preventing rejection of the fetus. Blood sugar: progesterone secreted by the placenta will increase the mother's blood sugar, which ultimately leads to an increase in the fetus's nutrient intake.
Progesterone is a steroid hormone with a carbon atom at position 21, containing a ketone group (C-3) and a double bond between C4 and C5. Usually, the detection of serum progesterone (PROG) is a polyclonal antibody prepared by immunoprecipitation using progesterone-11-hemisuccinate (P-11-HS) coupled to a carrier protein. PROG is a small molecule hapten and can only be used to prepare antibodies after being combined with a carrier. The traditional methods for quantitative detection of serum PROG are radioimmunoassay and ELISA. Among them, radioimmunoassay is currently the most widely used method, but its fatal disadvantages are its short validity period, cumbersome operation and environmental pollution. Therefore, people have been trying to find effective alternative methods for a long time. The ELISA method for detecting PROG solves the problems of radioimmunoassay to a certain extent, and by combining with chemiluminescence, it not only has the advantages of long validity period and simple operation, but also has higher sensitivity than radioimmunoassay, wider quantitative range, and more accurate and reliable quantitative analysis, which is an ideal method to replace radioimmunoassay.
Alternative Names
P4
4-Pregnene-3,20-dione
Pregn-4-ene-3,20-dione
Pregn-4-en-3,20-dione
References
- 1. Jewson M, et al. Progesterone and abnormal uterine bleeding/menstrual disorders. Best Pract Res Clin Obstet Gynaecol. 2020, 69:62-73.
References
Progesterone and abnormal uterine bleeding/menstrual disorders
Best Pract Res Clin Obstet Gynaecol
Authors: Jewson M, Purohit P, Lumsden MA
Abstract
This chapter explores the role of progesterone and progestogens in the management of abnormal uterine bleeding (AUB). Progestogens are used to regulate intermenstrual bleeding and decrease heavy menstrual bleeding (HMB) in women of reproductive age or who are perimenopausal. In menopausal women, progesterones and progestogens prevent endometrial hyperplasia and aim to reduce the development of endometrial cancer. We hope to make clear current best practice including preparation, specific benefits and risks. Progesterone also acts in concert with other hormones to affect breast, cardiovascular system, lipid profile and bone. We hope to explain how its unintended side effects may be used beneficially or may cause intended side effects.
Progesterone, reproduction, and psychiatric illness
Best Pract Res Clin Obstet Gynaecol
Authors: Standeven LR, McEvoy KO, Osborne LM
Abstract
Mood and anxiety disorders are vastly overrepresented in women, and one important contributor to these differences is the fluctuation in sex steroids in women during the reproductive years. Considerable evidence supports a role for abnormal sensitivity to these hormonal fluctuations for some women, who develop mood symptoms associated with reproductive transitions. This chapter presents evidence of the role of endogenous progesterone and its metabolites in such mood symptoms, and then goes on to cover the evidence concerning exogenous progesterone's effects on mood. Overall, the literature does not support an association between exogenous progesterone and negative mood in the general population, but does indicate that subset of women may be vulnerable to such effects. Research is lacking on women with psychiatric illness.
Progesterone and neuroprotection
Horm Behav.
Authors: Singh M, Su C
Abstract
Numerous studies aimed at identifying the role of estrogen on the brain have used the ovariectomized rodent as the experimental model. And while estrogen intervention in these animals has, at least partially, restored cholinergic, neurotrophin and cognitive deficits seen in the ovariectomized animal, it is worth considering that the removal of the ovaries results in the loss of not only circulating estrogen but of circulating progesterone as well. As such, the various deficits associated with ovariectomy may be attributed to the loss of progesterone as well. Similarly, one must also consider the fact that the human menopause results in the precipitous decline of not just circulating estrogens, but in circulating progesterone as well and as such, the increased risk for diseases such as Alzheimer's disease during the postmenopausal period could also be contributed by this loss of progesterone. In fact, progesterone has been shown to exert neuroprotective effects, both in cell models, animal models and in humans. Here, we review the evidence that supports the neuroprotective effects of progesterone and discuss the various mechanisms that are thought to mediate these protective effects. We also discuss the receptor pharmacology of progesterone's neuroprotective effects and present a conceptual model of progesterone action that supports the complementary effects of membrane-associated and classical intracellular progesterone receptors. In addition, we discuss fundamental differences in the neurobiology of progesterone and the clinically used, synthetic progestin, medroxyprogesterone acetate that may offer an explanation for the negative findings of the combined estrogen/progestin arm of the Women's Health Initiative-Memory Study (WHIMS) and suggest that the type of progestin used may dictate the outcome of either pre-clinical or clinical studies that addresses brain function.