Progesterone
Progesterone is a steroid hormone synthesized primarily from Cholesterol by the corpus luteum (after ovulation), the placenta (during pregnancy), and in smaller amounts by the adrenal cortex and brain (where it acts as a neurosteroid). It belongs to the progestogen class of steroids.
Hormonal fluctuations across the menstrual cycle: progesterone (yellow) rises sharply in the luteal phase after ovulation and falls if no implantation occurs
Synthesis
Like all steroid hormones, progesterone is derived from cholesterol:
Cholesterol → Pregnenolone → Progesterone (via 3β-HSD)
Progesterone can be further converted to cortisol, aldosterone, and Testosterone/estrogens — it is a key intermediate in steroidogenesis.
Role in the Menstrual Cycle
The menstrual cycle is divided by ovulation into two phases:
| Phase | Dominant Hormone | Uterine State |
|---|---|---|
| Follicular (days 1–14) | Estrogen | Endometrium proliferates |
| Luteal (days 15–28) | Progesterone | Endometrium secretes (prepares for implantation) |
After ovulation, the ruptured follicle becomes the corpus luteum, which secretes progesterone. This prepares the endometrium for embryo implantation. If no fertilization occurs, the corpus luteum degenerates (~day 24), progesterone drops, and menstruation begins.
Role in Pregnancy
If implantation occurs, the embryo secretes hCG (human chorionic gonadotropin), which rescues the corpus luteum and maintains progesterone production until the placenta takes over (~week 10). Progesterone during pregnancy:
- Maintains uterine quiescence (prevents premature contractions)
- Promotes uterine blood flow
- Suppresses maternal immune rejection of the fetus (immune tolerance)
- Stimulates breast development (with prolactin)
A sharp drop in progesterone triggers labor at term.
Neurosteroid Effects: Calming via GABA
Progesterone is metabolized in the brain to allopregnanolone (3α,5α-THPROG), a potent positive allosteric modulator of GABAA receptors — the same mechanism as benzodiazepines and alcohol.
- Allopregnanolone → anxiolytic, sedative, anticonvulsant, analgesic effects
- Explains premenstrual mood changes: in some women, the rapid progesterone drop before menstruation reduces allopregnanolone → anxiety, irritability (PMS/PMDD)
- Brexanolone (Zulresso): synthetic allopregnanolone, FDA-approved for postpartum depression — rapid-acting antidepressant acting on GABAA receptors
This is also why pregnancy often reduces seizure frequency in epilepsy (high progesterone/allopregnanolone), while premenstrual and postpartum periods can worsen seizures.
Contraception: Progestins
Synthetic progestins (progesterone analogs) are the key ingredient in:
- Combined oral contraceptives (with estrogen): suppress LH surge → no ovulation
- Progestin-only pills (“mini-pill”): thicken cervical mucus, thin endometrium
- Hormonal IUDs (Mirena): release levonorgestrel locally → suppress endometrium
- Implants (Nexplanon): sustained progestin release → suppresses ovulation
Postpartum Role
After delivery, rapid progesterone withdrawal is a trigger for postpartum mood changes and can contribute to postpartum depression via the allopregnanolone mechanism described above. This is why brexanolone (IV allopregnanolone replacement) is effective in postpartum depression.
Links to Other Steroids
Progesterone sits at the center of the steroidogenesis pathway:
- Downstream of: Cholesterol, pregnenolone
- Upstream of: Testosterone, cortisol, aldosterone, estrogens
see also
Tags: HormoneNeurotransmitter science ai-generated
Superlink: 052 🫧Hormone und Neurotransmitter
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Erstellt: 01-09-22 11:16