Disease relevance of DIHYDROPROGESTERONE

• Testosterone, progesterone, 17 alpha-hydroxyprogesterone, and 20 alpha-dihydroprogesterone have been measured in the spermatic and peripheral venous blood of 17 prepubertal boys undergoing surgery for undescended testis or inguinal hernia repair [1].
• We have assessed whether chronic treatment with progesterone (P), dihydroprogesterone (DHP) or tetrahydroprogesterone (THP) had neuroprotective effects against streptozotocin (STZ)-induced diabetic neuropathy at the neurophysiological, functional, biochemical and neuropathological levels [2].
• The aim of the present study was to evaluate the synthesis of dihydroprogesterone (DHP), tetrahydroprogesterone (THP), and the activity of 5alpha-reductase (5alphaR) which regulates the reduction of P to DHP on exposure to supraphysiological levels of E2 in vitro (C6 glioma cells) and in vivo (mouse brain) [3].
• Membrane 5alpha-pregnane-3,20-dione (5alphaP) receptors in MCF-7 and MCF-10A breast cancer cells are up-regulated by estradiol and 5alphaP and down-regulated by the progesterone metabolites, 3alpha-dihydroprogesterone and 20alpha-dihydroprogesterone, with associated changes in cell proliferation and detachment [4].
• The levels of the neuroactive steroids allopregnanolone (THP) and 5alpha-dihydroprogesterone (DHP) were quantified in the plasma of 11 (group 1) and in the liquor of 12 (group 2) Parkinson's disease (PD) patients using a gas-chromatographic/mass-spectrometric method [5].

High impact information on DIHYDROPROGESTERONE

• A second 17 beta-HSD isoform (referred to as type 2) is localized in the endoplasmic reticulum of human trophoblast and is characterized by the preferential oxidation of the C-17 beta-hydroxyl group of C18- and C19-steroids and the C-20 alpha-hydroxyl group of 20 alpha-dihydroprogesterone [6].
• A crucial biochemical reaction in vertebrates is progesterone conversion into neuroactive metabolites such as dihydroprogesterone (5alpha-DHP) and tetrahydroprogesterone (3alpha,5alpha-THP), which regulate several neurobiological processes, including stress, depression, neuroprotection, and analgesia [7].
• Suppression of ARK1C1 and AKR1C2 by selective small interfering RNAs inhibited production of 20alpha-dihydroprogesterone and was associated with increased progesterone in MCF-10A cells [8].
• The enzyme also demonstrated 20 alpha-HSD activity toward 20 alpha-dihydroprogesterone [9].
• 20alpha-Hydroxysteroid dehydrogenase (20alpha-SDH), an enzyme which reduces progesterone to 20alpha-dihydroprogesterone, was found to be associated with T lymphocytes [10].

Biological context of DIHYDROPROGESTERONE

• Rat ovarian 20 alpha-hydroxysteroid dehydrogenase plays a pivotal role in leuteolysis and parturition by catalysing the reduction of progesterone to give the progestationally inactive steroid 20 alpha-hydroxyprogesterone [11].
• Neuraminidase treatment also eliminated the ability of ovine FSH to increase ovarian weight, to induce ovulation, and to elevate serum progesterone and 20alpha-dihydroprogesterone [12].
• On the eighth day of pseudopregnancy, serum progesterone levels were decreased at 0.5 h after cloprostenol injection and fell further at 3 h; serum 20 alpha-dihydroprogesterone levels were first increased at 7 h after cloprostenol injection [13].
• Measurement of urinary oestrogens and 20 alpha-dihydroprogesterone during ovarian cycles of black (Diceros bicornis) and white (Ceratotherium simum) rhinoceroses [14].
• Plasma concentrations of progesterone and 17 alpha-hydroxyprogesterone were high in the 2nd and 3rd months of gestation, but 20 alpha-dihydroprogesterone increased from a level of 2 ng/ml, during the first 3 months, to 10-15 ng/ml during months 5-10, to reach 80-120 ng/ml during the last 30 days before foaling [15].

Anatomical context of DIHYDROPROGESTERONE

• Testosterone concentration in testes of 23 men, ages 51 to 90, was determined as 490 +/- 172 ng/g tissue (M +/- S.D.) and 20 alpha-dihydroprogesterone concentration as 10.0 +/- 2.3 ng/g tissue (M +/- S.D.) in 18 men of the same patient group [16].
• Progesterone and its derivatives dihydroprogesterone and tetrahydroprogesterone reduce myelin fiber morphological abnormalities and myelin fiber loss in the sciatic nerve of aged rats [17].
• These findings suggest that this 37K protein is not associated with either follicular or luteal cells, but, rather, is linked with the 20 alpha-hydroxyprogesterone-secreting interstitial gland cell population [18].
• Granulosa cells cultured for 2 days with PACAP-27, VIP, or GHRH (10(-9)-10(-6) M) showed dose-dependent increases in the accumulation of progesterone, 20 alpha-dihydroprogesterone, and estrogen [19].
• The most obvious change is an increase in the ability of the cultured cells to synthesize 20 alpha-dihydroprogesterone (20 alpha-hydroxypregn-4-en-3-one) [20].

Associations of DIHYDROPROGESTERONE with other chemical compounds

• Concentrations of 16 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone were unchanged by cortisol infusion initially (P greater than 0.1) and with retreatment and increased treatment time (P greater than 0.1) [21].
• Within 3 h after the administration of P, the initial content and the in vitro production rate of P, testosterone, and 17 beta-estradiol by antral follicles decreased in the P-treated animals compared to that in follicles of control animals, whereas the follicular content the production rate of 20 alpha-dihydroprogesterone were unaffected [22].
• Distribution of progesterone receptor, estradiol dehydrogenase, and 20 alpha-dihydroprogesterone dehydrogenase activities in human endometrial glands and stroma: progestin induction of steroid dehydrogenase activities in vitro is restricted to the glandular epithelium [23].
• Cytochalasin does not inhibit the conversion of pregnenolone to 20alpha-dihydroprogesterone but was shown to inhibit increased transport of [3H]cholesterol to mitochondria resulting from the action of ACTH [24].
• Both rec preparations of 20 alpha HSD demonstrated a single polypeptide chain of 37 kDa with similar K(m) values for 20 alpha-hydroxyprogesterone and NADP, although the corresponding maximum velocity values were slightly lower for the rec 20 alpha HSD expressed in the insect cells [25].

Gene context of DIHYDROPROGESTERONE

• The steroidogenic enzyme 20 alpha HSD regulates the conversion of progesterone to 20 alpha-hydroxyprogesterone in many mammalian species [26].
• Data obtained in our and other laboratories have indicated that progesterone (P) and its derivatives, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), stimulate the expression of two myelin proteins of the peripheral nervous system (PNS) [i.e., glycoprotein zero (P0) and peripheral myelin protein 22 (PMP22)] [27].
• Moreover, a lack of neuroprotective factors (i. e., GDNF, BDNF), promoted by DHP, may contribute to dopaminergic cell death [5].
• At pH 9.0, apparent Michaelis constants were 0.8, 1.3, and 2.3 microM for estradiol-17 beta, testosterone, and 20 alpha-dihydroprogesterone, respectively, 17 beta-HSD activity with testosterone was inhibited by estradiol-17 beta, 5 alpha-dihydrotestosterone, 5 beta-dihydrotestosterone, 20 alpha-dihydroprogesterone, and progesterone [28].
• In the latter case, progesterone secretion was maintained and 20 alpha-dihydroprogesterone secretion fell suggesting an inhibitory action by PRL against 20 alpha-hydroxysteroid dehydrogenase activity [29].

Analytical, diagnostic and therapeutic context of DIHYDROPROGESTERONE

• The total contents of progesterone and 20 alpha-dihydroprogesterone in flasks were determined after the incubation periods by radioimmunoassay [30].
• The development of a sensitive enzyme-immunoassay for 20 alpha-dihydroprogesterone (20 alpha-DHP) and its use in determining reproductive status in black and white rhinoceroses is reported [14].
• All women were given hormone replacement therapy with transdermal oestradiol, either patch (50 microg/24 h) or gel (1 mg/day), cyclically combined with oral dihydrogesterone (10 mg/day for 12 days/month, on days 19-30 of the month) [31].
• High performance liquid chromatography (HPLC) separations confirmed that progesterone and 20alpha-dihydroprogesterone predominated in the plasma, whereas in the feces several unconjugated, immunoreactive progestagen metabolites containing either a 20-oxo- or a 20alpha-OH-group occurred [32].
• Yellow perch ovarian tissue converted [14C]progesterone or [14C]pregnenolone to six metabolites that were effective in inducing GVBD in the bioassays: 5 alpha-pregnanedione, 17 alpha-hydroxyprogesterone, 20 alpha-dihydroprogesterone, 17 alpha-hydroxy, 20 alpha-dihydroprogesterone (tentatively identified), and two other unidentified metabolites [33].

References