Pregnanediol Glucuronide (PdG) [BSA]

Progesterone is an endogenous steroid and it that is necessary to maintain pregnancy. Progesterone is the main component of progestogen. It is mainly synthesized by the placenta during pregnancy in women, secreted by the ovaries during non-pregnancy, and mainly synthesized by Leydig cells and adrenal cortex in men. The synthesis of progesterone requires the action of a variety of hydroxylases and aromatase, among which there are three key enzymes: 17α⁃hydroxylase, 21⁃hydroxylase and 11β⁃hydroxylase. Under their action, progesterone can be converted into Sex hormones, glucocorticoids and mineralocorticoids. The synthesis of progesterone mainly depends on cholesterol. Cholesterol is converted into progesterone in the ovaries, placenta, adrenal glands and other parts under the action of various enzymes. Therefore, cholesterol levels have an important impact on the synthesis of progesterone. Too high or too low cholesterol may lead to abnormal progesterone. Progesterone has a wide range of functions. It is not only involved in the female menstrual cycle and pregnancy, but also involves male reproductive function and physical health.

Figure 1. Salivary Estrone -1-Glucuronide and Pregnanediol -3- Glucuronide
concentration analytes during different phases of menstrual cycle.(Source: Alagendran et al., 2022)

Regulation of the menstrual cycle: Progesterone plays a key role in the female menstrual cycle. Together with estrogen, it regulates the balance of the hypothalamic-pituitary-ovarian axis and affects the development of follicles and the timing of ovulation. When the ovary ovulates in the middle of menstruation, the follicle that releases the egg forms a corpus luteum, which secretes progesterone. Progesterone converts the endometrium from the proliferative phase to the secretory phase, maintaining its thickness until menstruation. At this time, the corpus luteum shrinks, the progesterone concentration in the blood drops sharply, and the endometrium peels off to form menstruation. If ovulation does not occur, the corpus luteum will not form, progesterone will not rise, the endometrium will not transition into the secretory phase, and menstruation will not occur. Maintaining pregnancy: Progesterone plays a more important role in pregnancy and is necessary to maintain pregnancy. After the fertilized egg implants in the uterus, progesterone will continue to maintain the secretion state of the endometrium to provide nutrition and protection for the embryo. Progesterone also inhibits uterine contractions, preventing the embryo from falling out or miscarriage. Progesterone also suppresses the mother's immune response and prevents rejection of the embryo. Progesterone also promotes breast development in preparation for breastfeeding. Progesterone levels continue to increase during pregnancy, from 5-40 ng/ml in the luteal phase to 100-200 ng/ml in the third trimester. If progesterone levels are too low, it may lead to complications such as early miscarriage, fetal arrest, and premature birth. Affects psychological state: Progesterone not only affects physiology, but also affects psychology. Progesterone is a neurosteroid that can pass through the blood-brain barrier and act on multiple areas of the brain to regulate mood, cognition, sleep, memory and other functions. Changes in progesterone levels can lead to changes in women's psychological state. Generally speaking, an increase in progesterone can make a woman feel calm, secure, and happy, while a decrease in progesterone can make a woman feel anxious, depressed, and irritable. This is why women's emotions are relatively stable during premenstrual and pregnancy periods, while women's emotions are more volatile during late menstruation and postpartum period. Participate in the synthesis of androgens: The role of progesterone in men cannot be ignored. It is an important precursor of androgens. Androgens are the main male sex hormones, affecting male reproductive organs, secondary sexual characteristics, sexual function, skeletal muscles, etc . The synthesis of androgens mainly occurs in the Leydig cells of the testis and requires multiple steps, of which progesterone is a key intermediate. Progesterone can be converted into androstenediol, then into testosterone, and finally into dihydrotestosterone. If the level of progesterone is too low, it will affect the synthesis of androgens, leading to reduced male sexual function, poor development of reproductive organs, and reduced skeletal muscle.

Regulating the function of the nervous system: Progesterone also plays an important role in the male nervous system. It can act as a neuroprotective factor to protect neurons from damage and promote the regeneration and repair of neurons. Progesterone can also regulate the release of neurotransmitters and receptor sensitivity, affecting mood, cognition, sleep, memory and other functions. Changes in progesterone levels can lead to changes in men's psychological states. Generally speaking, an increase in progesterone can make a man feel calm, secure, and happy, while a decrease in progesterone can make a man feel anxious, depressed, and irritable. This is why men tend to be more emotionally unstable under stress or in old age. Pregnanediol-3-glucuronide (PdG) is a progesterone metabolite. It is metabolized by progesterone in the liver into inactive pregnanediol and then combined with glucuronic acid and excreted in the urine. Therefore, PdG is an inactive product formed when the body breaks down progesterone. The study found that researchers could infer progesterone levels by measuring the levels of pregnadiol in urine. This also indirectly provides a way to measure progesterone levels in the body.

Pregnanediol-3α-glucuronide
Pregnanediol-3-glucuronide
PdG
PdG Antigen