- Progesterone Receptor (PR) - High binding affinity (Kᵢ = 0.2–0.5 nM) [13]
- Activates PR-mediated transcription without androgenic/estrogenic effects [13]
- 5α-Reductase - Inhibits 5α-reductase type 2 (Kᵢ = 2.1 μM) [13]
- Neurosteroid Biosynthesis - Induces allopregnanolone production in brain and serum [6]

强效口服孕激素（如屈孕酮）可用于治疗一系列与孕酮水平低相关的妇科疾病。尽管具有与天然黄体酮相当的药理学特征和化学结构。即使剂量小得多，它也具有口服作用。与大多数其他合成孕激素相比，它具有不含雌激素、雄激素、合成代谢、皮质类固醇和其他负面激素影响的额外优势。此外，使用睾酮的雌激素替代治疗（HRT）被批准用于预防无对抗雌激素对子宫完整的女性子宫内膜的破坏性影响。除了普遍耐受性良好和安全之外，地孕酮还缺乏与其他孕激素（如甲羟孕酮）相关的一些雄激素副作用[1]。

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1. PR介导的转录激活 - 细胞系：转染PR荧光素酶报告基因的人子宫内膜癌细胞（Ishikawa）。 - 处理：Dydrogesterone（0.1–10 μM）处理24小时。 - 结果： - EC₅₀ = 0.8 μM（PR激活）[13]
- 不激活雄激素受体（AR）或糖皮质激素受体（GR）[13]
2. 5α-还原酶抑制 - 酶来源：重组人5α-还原酶2型。 - 处理：与Dydrogesterone（0.1–10 μM）和[³H]-睾酮（1 nM）在37°C孵育1小时。 - 结果： - Kᵢ = 2.1 μM（抑制5α-双氢睾酮生成）[13]
- 10 μM时抑制率>50%[13]
3. 神经甾体调节 - 细胞系：大鼠海马神经元暴露于Dydrogesterone（1–10 μM）48小时。 - 结果： - 别孕烯醇酮水平升高2–3倍（LC-MS/MS）[6]
- γ-氨基丁酸（GABA）受体亚基表达上调[6]

1. 应激诱导流产的预防 - 动物模型：CBA/J雌鼠与DBA/2J雄鼠交配，妊娠第5天施加应激。 - 处理：应激前单次腹腔注射Dydrogesterone（1–5 mg/kg）。 - 结果： - 流产率从65%（对照组）降至18%（5 mg/kg）[5]
- 血浆孕激素诱导阻断因子（PIBF）升高2.5倍[5]
- Th1/Th2平衡向Th2偏移（IL-4↑，IFN-γ↓）[5]
2. 骨代谢调节 - 动物模型：去卵巢大鼠口服Dydrogesterone（0.1–1 mg/kg/天）12周。 - 结果： - 骨密度（BMD）维持正常（DEXA扫描）[3]
- 破骨细胞活性降低（抗酒石酸酸性磷酸酶，TRAP）[3]
3. 脑内神经甾体生成 - 动物模型：雌性大鼠口服Dydrogesterone（1 mg/kg/天）2周。 - 结果： - 额叶和海马别孕烯醇酮水平分别升高40%和35%[6]
- 高架十字迷宫测试焦虑行为改善[6]

1. 孕激素受体结合实验 - 试剂：人子宫胞浆、[³H]-孕酮（1 nM）、Dydrogesterone。 - 流程： - 胞浆与[³H]-孕酮及Dydrogesterone（0.01–1 μM）在4°C孵育2小时。 - 葡聚糖包被活性炭分离结合配体。 - 分析：Dydrogesterone置换[³H]-孕酮的亲和力高于孕酮（Kᵢ = 0.2 nM）[13]
2. 5α-还原酶活性实验 - 试剂：重组人5α-还原酶2型、NADPH、[³H]-睾酮（1 nM）。 - 流程： - 酶与Dydrogesterone（0.1–10 μM）及底物在37°C反应60分钟。 - 乙酸乙酯终止反应，液闪计数检测DHT生成。 - 结果：Dydrogesterone抑制5α-还原酶（Kᵢ = 2.1 μM）[13]

1. 子宫内膜细胞增殖抑制 - 细胞系：人子宫内膜基质细胞（HESC）经Dydrogesterone（0.1–10 μM）处理72小时。 - 检测： - MTT法：IC₅₀ = 3.5 μM[13]
- Western Blot：下调周期蛋白D1和PCNA表达[13]
- TUNEL法：凋亡率从8%升至22%[13]
2. 神经元神经甾体诱导 - 细胞系：大鼠原代海马神经元暴露于Dydrogesterone（1 μM）48小时。 - 检测： - LC-MS/MS：别孕烯醇酮水平升高2.8倍[6]
- qPCR：类固醇生成急性调节蛋白（StAR）mRNA上调[6]

1. Stress-Induced Abortion Model - Animal: Pregnant CBA/J mice (day 5 post-coitus). - Treatment: - Dydrogesterone (1–5 mg/kg, intraperitoneal) administered 1 hour before sound stress (95 dB, 30 minutes). - Control groups: vehicle-treated stressed mice and non-stressed mice. - Assessment: - Abortion rate calculated on day 13 [5]
- Plasma PIBF levels measured by ELISA [5]
- Uterine tissue analyzed for Th1/Th2 cytokine expression [5]
2. Osteoporosis Prevention in Rats - Animal: Ovariectomized Sprague-Dawley rats (200–250 g). - Treatment: - Dydrogesterone (0.1–1 mg/kg/day, oral) dissolved in corn oil for 12 weeks. - Control groups: sham-operated and vehicle-treated ovariectomized rats. - Assessment: - BMD measured by dual-energy X-ray absorptiometry (DEXA) [3]
- Serum osteocalcin and TRAP levels analyzed by colorimetry [3]

Absorption, Distribution and Excretion
Rapidly absorbed in the gastrointestinal tract, with a bioavailability of 28%. Following oral administration of labeled dydrogesterone, an average of 63% of the dose is excreted in the urine. Excretion is completed within 72 hours. Following oral administration of dydrogesterone, plasma concentrations of dihydrodydrogesterone (DHD) are significantly higher than those of the mother. The AUC and Cmax ratios of DHD to dydrogesterone are approximately 40 and 25, respectively. DHD is rapidly absorbed. The Tmax values for dydrogesterone and DHD range from 0.5 to 2.5 hours. The hemolytic concentration of dihydrodydrogesterone is 13 ng/mL, with a Cmin of 4.1 ng/mL and a Cmax of 63 ng/mL. The hemolytic concentration of dydrogesterone is 0.38 ng/mL, with a Cmin <0.1 ng/mL and a Cmax of 2.5 ng/mL. It has been reported that the progesterone is distributed into breast milk. The potential effects of progestins in breast milk on breastfed infants have not been determined. /Progestin Overview/

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Metabolism/Metabolites
Dydrogesterone is completely metabolized to 20-dihydrodydrogesterone (DHD) metabolites.
In the human body, dydrogesterone is completely metabolized. The major metabolite of dydrogesterone is 20α-dihydrodydrogesterone (DHD), which is mainly present in urine as a glucuronide conjugate. A common characteristic of all identified metabolites is that they retain the 4,6-dien-3-one configuration of the parent compound and lack 17α-hydroxylation. This explains their lack of estrogenic and androgenic activity.
Dydrogesterone is not excreted in urine as pregnanediol like progesterone. Therefore, it remains feasible to analyze endogenous progesterone production based on pregnanediol excretion.

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Biological Half-Life
Dydrogesterone: 5-7 hours, 20-dihydrodydrogesterone (DHD) metabolite: 14-17 hours
The mean terminal half-lives of dydrogesterone and DHD are 5 to 7 hours and 14 to 17 hours, respectively.

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- Absorption: - Rapid oral absorption; peak plasma concentration (Cₘₐₓ) is reached within 2-3 hours [7]
- Absolute bioavailability: approximately 28-30% in humans [7]
- Metabolism: - Primarily metabolized in the liver by aldosterone reductase 1C (AKR1C) to 20α-dihydrodydrogesterone [7]
- A small amount is metabolized by CYP3A4 (contributing 20-30%) [7]
- Half-life: - Terminal half-life (t₁/₂): 5-7 hours in humans [7]
- Excretion: - 60-70% is excreted in urine as conjugates; 20-30% is excreted in feces [7]

Acute toxicity: - LD₅₀: >5000 mg/kg (oral in rats)[9] - Subchronic toxicity: - No significant hepatotoxicity or nephrotoxicity was observed in rats at daily doses up to 10 mg/kg[9] - No genotoxicity or carcinogenicity was found in animal studies[9] - Plasma protein binding: - Approximately 93% bound to sex hormone-binding globulin (SHBG)[10]

[1]. Dydrogesterone, From Wikipedia, the free encyclopedia.

Dydrogesterone is a 3-oxo-Δ⁴ and 20-oxosteroid with progestin activity. It is a synthetic progestin without androgenic or estrogenic activity. Unlike many other progestins, dydrogesterone does not cause a rise in body temperature or inhibit ovulation. It is a synthetic progestin without androgenic or estrogenic activity. Unlike many other progestins, dydrogesterone does not cause a rise in body temperature or inhibit ovulation. Indications: Used to treat irregular menstrual cycles and menstrual disorders caused by progesterone deficiency. Also used to prevent spontaneous abortion in patients with a history of recurrent miscarriage. Mechanism of Action: Dydrogesterone is a progestin that regulates the healthy growth and normal shedding of the endometrium by acting on progesterone receptors in the uterus. Dydrogesterone is an orally effective progestin. For women who have not undergone hysterectomy, progesterone supplementation can significantly reduce estrogen-induced endometrial hyperplasia and the risk of cancer by decreasing endometrial growth. Progesterone should not be equated with progesterone, as some progesters have estrogenic activity, some have mild androgenic activity, and some are purely progesterone; correspondingly, their mechanisms of ovulation inhibition may differ slightly. On the other hand, 17-hydroxy or acetoxy compounds elicit responses closer to progesterone. They have little or no estrogenic or androgenic activity and may produce catabolic and mild diuretic effects. 19-normethyl derivatives are more effective in delaying normal menstruation. Increasing evidence suggests that substance P (SP) is involved in neurogenic inflammation and pain perception primarily through its high-affinity neurokinin 1 receptor (NK-1R). Interestingly, decreased pain sensitivity is associated with elevated plasma progesterone levels. We hypothesize that progesterone may attenuate nociception and associated inflammatory responses through an NK-1R-dependent pathway. To test our hypothesis, we incubated splenic lymphocytes from female CBA/J mice with different concentrations of the progesterone derivative dydrogesterone. We then analyzed the expression of NK-1R and T helper (Th1) cytokines using flow cytometry. Next, we subcutaneously injected 1.25 mg of dydrogesterone (dissolved in 200 μL of sesame oil) into CBA/J mice; control mice received a sham injection. A tail-flick test was performed every 30 minutes after injection to detect the pain threshold. Lymphocytes were isolated from blood and the uterus, and their NK-1R surface expression was analyzed. We performed immunohistochemical analysis to investigate the distribution of NK-1R in uterine tissue. Dydrogesterone reduced the percentage of NK-1R-positive lymphocytes both in vitro and in vivo. Furthermore, in vitro experiments showed that dydrogesterone treatment increased Th2 cytokine levels while decreasing Th1 cytokine levels. The prolonged tail-flick latency after dydrogesterone injection supports the view that decreased NK-1R expression on lymphocytes is associated with an increased pain threshold. In summary, these results clearly reveal the pathways by which dydrogesterone or progesterone regulates the interactions of the nervous, endocrine, and immune systems in inflammation and pain. For more complete data on the mechanisms of action of dydrogesterone (6 studies), please visit the HSDB records page.

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1. Mechanism of action: - PR-mediated transcription: Activates PR to induce decidualization and endometrial maturation [13]
- Immunomodulation: Promotes the Th2 cytokine spectrum to prevent fetal rejection [5]
- Neurosteroid production: Enhances the synthesis of allogeneic ketones to regulate GABAergic signaling [6]
2. Clinical applications: - Approved for: - Threatened/recurrent miscarriage (10-40 mg/day) [8]
- Endometriosis (10-30 mg/day) [8]
- Menopausal hormone therapy (10 mg/day) [8]
3. Side effects: - Common: Headache, dizziness, abdominal pain [10]
- Rare: Venous thromboembolism (incidence <0.1%) [10]

C21H28O2

312.45

312.208

C, 80.73; H, 9.03; O, 10.24

152-62-5

Levonorgestrel;797-63-7;Dydrogesterone-d6

9051

White to light yellow solid powder

1.1±0.1 g/cm3

462.8±45.0 °C at 760 mmHg

168-173°C

172.2±25.7 °C

0.0±1.1 mmHg at 25°C

1.557

3.58

34.14

0

2

1

23

628

6

CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@@H]3[C@H]2C=CC4=CC(=O)CC[C@@]34C)C

JGMOKGBVKVMRFX-HQZYFCCVSA-N

InChI=1S/C21H28O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h4-5,12,16-19H,6-11H2,1-3H3/t16-,17+,18-,19+,20+,21+/m0/s1

(8S,9R,10S,13S,14S,17S)-17-acetyl-10,13-dimethyl-1,2,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-one

Dydrogesterone; Isopregnenone; dydrogesterone; 152-62-5; Isopregnenone; Hydrogesterone; Duphaston; Hydrogestrone; Gynorest; Gestatron; Hydrogesterone; Duphaston; Hydrogestrone; Dufaston; Isopregnenone; Solvay Brand of Dydrogesterone

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~33.33 mg/mL (~106.67 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (8.00 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (8.00 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (8.00 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。