Pregnenolone

Pregnenolone is a naturally occurring steroidal hormone that serves as the biochemical “precursor” from which virtually all other steroid hormones are derived, including progesterone, cortisol, estrogen, and testosterone.

• Synthesized primarily in the adrenal cortex, brain, and gonads.
• Its primary purpose is to provide the foundational scaffold for the synthesis of downstream hormones that regulate stress, metabolism, cognition, and reproductive function.

Pregnenolone (IUPAC: (3β)-3‑hydroxy‑5‑pregnene‑20‑one) is a C₂₁ steroid (C₂₁H₃₀O₂, molar mass 316.46 g/mol).

• It features a characteristic sterane skeleton with:
  • a Δ⁵‑double bond between C5–C6
  • a ketone at C20
  • a hydroxyl group at C3 (β‑orientation).
• The molecule is lipophilic (log P ≈ 4.2) and poorly soluble in water but readily soluble in organic solvents (e.g., ethanol, oil).
• Its structural similarity to other steroid hormones enables conversion by enzymes such as 3β‑HSD, CYP17A1, and 5α‑reductase, allowing rapid interconversion with downstream steroids.
• The presence of the 3β‑hydroxyl group is crucial for binding to the progesterone receptor and for neurosteroid activity.

Commercial pregnenolone is produced primarily by chemical synthesis from commercially available steroids (e.g., diosgenin from yams or plant sterols) followed by controlled oxidation and purification.

• Natural extraction from animal adrenal tissue is rare due to low yield and ethical concerns.
• Most supplements use a fully synthetic, pharmaceutical‑grade product that meets USP/NF specifications for purity (≥ 98 %).
• Quality considerations include:
  • verification of the absence of residual solvents
  • heavy‑metal testing
  • confirmation of the correct stereochemistry (3β‑hydroxy).
• Third‑party certification (e.g., USP, NSF, or Informed‑Choice) is recommended to ensure consistency and to avoid inadvertent inclusion of estrogenic or androgenic contaminants.