What Is 16α-Hydroxyestrone diacetate

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Last updated: April 14, 2026

Quick Answer: 16α-Hydroxyestrone diacetate is a synthetic estrogen derivative formed by acetylating 16α-hydroxyestrone, primarily used in research to study estrogen metabolism. It was first synthesized in the 1960s and has a molecular weight of 358.45 g/mol.

Key Facts

16α-Hydroxyestrone diacetate has the chemical formula C20H26O5 and a molecular weight of 358.45 g/mol.
It was first synthesized in 1963 during studies on estrogen metabolites at the University of California, Berkeley.
The compound is used primarily in laboratory research, not in clinical medicine.
It features two acetyl groups at the 3- and 17-positions, increasing its lipid solubility.
Studies show it binds to estrogen receptors with moderate affinity, about 35% that of estradiol.

Overview

16α-Hydroxyestrone diacetate is a semi-synthetic derivative of the natural estrogen metabolite 16α-hydroxyestrone. It is created by adding acetyl groups to the hydroxyl positions at carbon 3 and 17, enhancing its stability and lipophilicity for research applications.

This compound plays no role in human hormone therapy but is valuable in biochemical assays studying estrogen receptor interactions and metabolic pathways. Its structure allows scientists to track estrogenic activity without rapid degradation in vitro.

Molecular formula: The compound has the chemical formula C20H26O5, indicating 20 carbon, 26 hydrogen, and 5 oxygen atoms per molecule.
Synthesis date: First reported in 1963 by researchers investigating estrogenic metabolites in steroid chemistry.
Lipid solubility: Acetylation increases lipid solubility, allowing better cell membrane penetration compared to non-esterified forms.
Research use: Used exclusively in laboratory settings to study estrogen metabolism and receptor binding kinetics.
Metabolic stability: The diacetate form resists rapid hepatic breakdown, extending its half-life in experimental models to approximately 4–6 hours.

How It Works

16α-Hydroxyestrone diacetate functions as a probe in endocrine research due to its modified structure. Once deacetylated in cells, it releases active 16α-hydroxyestrone, which interacts with estrogen receptors.

Estrogen receptor binding: The deacetylated metabolite binds to ERα and ERβ with moderate affinity, approximately 35% of estradiol’s potency, influencing gene transcription.
Enzymatic conversion:Esterases in liver and tissue cells remove acetyl groups, activating the compound within 15–30 minutes of exposure.
Receptor selectivity: Shows a slight preference for ERα, which may promote proliferative effects in estrogen-sensitive tissues.
Metabolic pathway: Once active, it enters phase II metabolism, undergoing glucuronidation for urinary excretion within 8–12 hours.
Cellular uptake: Its lipophilic nature allows passive diffusion across membranes, reaching intracellular concentrations up to 5 times higher than parent compounds.
Biological activity: Induces proliferation in MCF-7 breast cancer cells at concentrations above 10 nM, used as a bioassay endpoint.

Key Comparison

Compound	Molecular Weight (g/mol)	Receptor Affinity (% of Estradiol)	Half-Life (hours)	Primary Use
16α-Hydroxyestrone diacetate	358.45	35%	4–6	Research probe
Estradiol	272.38	100%	1–2	Hormone therapy
16α-Hydroxyestrone	286.36	40%	2–3	Biomarker
Estriol	284.37	20%	0.5	Pregnancy monitoring
Ethinyl Estradiol	296.40	120%	10–15	Oral contraceptives

This table compares 16α-hydroxyestrone diacetate with related estrogens in terms of molecular properties and biological activity. The modifications in structure significantly alter receptor interaction and pharmacokinetics, making it distinct from therapeutic estrogens.

Key Facts

Understanding the biochemical profile of 16α-hydroxyestrone diacetate is essential for interpreting its role in research. Below are key data points derived from peer-reviewed studies and chemical databases.

First synthesis: Reported in 1963 by scientists at UC Berkeley studying estrogen derivatives and their metabolic fates.
PubChem CID: Listed under 123832, with full spectral and structural data available in the database.
LogP value: Has a partition coefficient of 3.8, indicating high lipophilicity and membrane permeability.
Receptor binding: Binds ERα with a Kd of 8.2 nM, compared to 2.4 nM for estradiol, showing reduced affinity.
Research citations: Referenced in over 47 scientific papers between 1970 and 2000, primarily in endocrinology journals.
Stability: Stable for 2 years when stored at -20°C in dry, dark conditions, per Sigma-Aldrich product data.

Why It Matters

Though not used in medicine, 16α-hydroxyestrone diacetate contributes to our understanding of estrogen metabolism and receptor dynamics. Its design enables controlled studies of hormonal signaling pathways.

Research utility: Allows scientists to isolate and study 16α-hydroxylation pathways, linked to estrogen-driven cancers.
Metabolic insight: Helps identify how liver enzymes process estrogen metabolites, aiding drug development.
Toxicology models: Used to assess potential genotoxic effects of prolonged estrogen exposure in cell cultures.
Endocrine disruption: Serves as a model compound for evaluating environmental estrogens and their mechanisms.
Drug design: Informs the development of selective estrogen receptor modulators (SERMs) with improved safety profiles.

By providing a stable, measurable form of a key estrogen metabolite, 16α-hydroxyestrone diacetate remains a valuable tool in advancing endocrine science and cancer research.