Progesterone

1. Overview

Progesterone is a steroid hormone that plays a central role in the regulation of the female reproductive system, particularly in the menstrual cycle, implantation, and maintenance of pregnancy. It is often referred to as the “pregnancy hormone” due to its critical role in preparing and sustaining the endometrium for embryo implantation. Although primarily associated with female physiology, progesterone also has functions in males and acts on various non-reproductive tissues.

2. Location

Progesterone is synthesized in several endocrine and reproductive tissues:

• Ovaries: In non-pregnant women, progesterone is produced by the corpus luteum after ovulation.

• Placenta: During pregnancy, the placenta becomes the main source of progesterone.

• Adrenal cortex: Produces small amounts of progesterone in both sexes as part of corticosteroid synthesis.

• Testes: In males, Leydig cells produce low levels of progesterone as a precursor to testosterone.

• CNS and glial cells: Can produce neurosteroids, including progesterone, with potential roles in brain function.

3. Structure

Progesterone is a 21-carbon steroid hormone derived from cholesterol. It has a molecular formula of C21H30O2. It belongs to the class of progestogens and serves as the primary natural progestogen in the human body. It is synthesized through the enzymatic conversion of pregnenolone via 3β-hydroxysteroid dehydrogenase and acts through the intracellular progesterone receptor (PR), which is part of the nuclear receptor family.

4. Function

Progesterone has multiple physiological functions across different organ systems:

• Reproductive system:

  • Prepares the endometrium for implantation during the luteal phase of the menstrual cycle.

  • Maintains the endometrium during early pregnancy.

  • Suppresses uterine contractions to prevent early expulsion of the embryo.

• Mammary glands:

  • Promotes development of the lobuloalveolar system in preparation for lactation.

• CNS:

  • Acts as a neurosteroid involved in mood regulation, sleep, and neuroprotection.

• Metabolism:

  • Stimulates lipoprotein lipase, promotes fat deposition, and modulates insulin sensitivity.

5. Physiological role(s)

Progesterone plays vital roles throughout the female reproductive lifespan:

• Menstrual cycle: Secreted after ovulation by the corpus luteum; it transforms the proliferative endometrium into a secretory lining ready for embryo implantation.

• Early pregnancy: Supports early gestation by maintaining the uterine lining and modulating the maternal immune response to tolerate the embryo.

• Late pregnancy: Helps suppress uterine contractility and is involved in breast development.

• Parturition: Withdrawal of progesterone activity near term is associated with the onset of labor.

• Neurophysiology: May reduce anxiety, modulate pain perception, and protect neurons against injury.

6. Clinical Significance

Altered progesterone levels or receptor function can result in various reproductive and systemic disorders:

• Luteal phase deficiency:

  • Inadequate progesterone secretion post-ovulation can impair implantation and contribute to infertility or early miscarriage.

• Menstrual disorders:

  • Low progesterone levels may result in irregular cycles, premenstrual syndrome (PMS), or heavy menstrual bleeding.

• Pregnancy support:

  • Progesterone supplementation is used in assisted reproductive technologies (ART) and to reduce risk of recurrent pregnancy loss.

• Hormone replacement therapy (HRT):

  • Progesterone is used in HRT regimens to prevent estrogen-induced endometrial hyperplasia in postmenopausal women.

• Contraception:

  • Synthetic progestins (progesterone analogs) are used in various contraceptive methods, including pills, injections, implants, and IUDs.

• Progesterone receptor modulators:

  • Drugs like mifepristone act as progesterone antagonists and are used for medical termination of pregnancy and fibroid treatment.

• Neuroprotective applications:

  • Experimental use of progesterone in traumatic brain injury and neurodegenerative conditions is under investigation.