Efficacy Of 17- Α-Hydroxy-Progestrone In Prevention Of Preterm Labour In High Risk Pregnant Women.

BACKGROUND: Preterm delivery (before 37 completed weeks of gestation) is a major determinant of infant mortality. The objective of study was to determine the efficacy of 17-alpha hydroxyprogesterone in preventing delivery before 37 weeks of gestation in high risk women. METHODS: This study, a randomized controlled trial was conducted in Obstetrics OPD, observing all scientific and ethical protocols. The women with less than 20 weeks gestation and with a past history of preterm delivery were included. A total of 132 women fulfilled the study requirements. Two groups made were as follows: Group A (Treatment group received intramuscular 17-alpha hydroxy-progesterone) and Group B served as control (The control group revived intramuscular Neurobion). A total of 66 women were assigned to each group. The data was recorded on a specially designed proforma for statistical analysis and comparison following the standard procedure. RESULTS: The criterion was strictly observed. The results showed a statistically significant (p<0.01) difference between group A as compared to group B. CONCLUSIONS: 17-α- Hydroxyprogesterone was found to be an effective drug in preventing delivery before 37 weeks in women at risk.

Protein-ligand docking using FFT based sampling: D3R case study.

Fast Fourier transform (FFT) based approaches have been successful in application to modeling of relatively rigid protein-protein complexes. Recently, we have been able to adapt the FFT methodology to treatment of flexible protein-peptide interactions. Here, we report our latest attempt to expand the capabilities of the FFT approach to treatment of flexible protein-ligand interactions in application to the D3R PL-2016-1 challenge. Based on the D3R assessment, our FFT approach in conjunction with Monte Carlo minimization off-grid refinement was among the top performing methods in the challenge. The potential advantage of our method is its ability to globally sample the protein-ligand interaction landscape, which will be explored in further applications.

Selected cholesterol biosynthesis inhibitors produce accumulation of the intermediate FF-MAS that targets nucleus and activates LXRα in HepG2 cells.

Sterol intermediates of the cholesterol biosynthetic pathway have drawn attention for novel biological activities. Follicular fluid meiosis activating sterol (FF-MAS) is a LXRα ligand and a potential modulator of physiologic processes regulated by nuclear receptors, such as lipid homeostasis and cell proliferation. In this work, we established a model to selectively accumulate FF-MAS in HepG2 cells, by using a combination of the inhibitors AY9944 and 17-hydroxyprogesterone to block C14-sterol reductases and the downstream C4-demethylase complex. We investigated the effects produced by altered levels of cholesterol biosynthesis intermediates, in order to dissect their influence on LXRα signaling. In particular, endogenously accumulated FF-MAS was able to modulate the expression of key genes in cholesterol metabolism, to activate LXRα nuclear signaling resulting in increased lipogenesis, and to inhibit HepG2 cells proliferation. Moreover, a fluorescent ester derivative of FF-MAS localized in nuclear lipid droplets, suggesting a role for these organelles in the storage of signaling lipids interacting with nuclear partners.

Progesterone, Inflammatory Cytokine (TNF-α), and Oxidative Stress (H2O2) Regulate Progesterone Receptor Membrane Component 1 Expression in Fetal Membrane Cells.

Progesterone receptor membrane component 1 (PGRMC1) is an important novel mediator of progesterone (P4) function in fetal membrane cells. We demonstrated previously that PGRMC1 is differentially expressed in fetal membranes among pregnancy subjects and diminished in preterm premature rupture of membrane subjects. In the current study, we aim to elucidate whether PGRMC1 expression is regulated by P4, tumor necrosis factor α (TNF-α), and H2O2 in fetal membrane cells. Primary cultured membrane cells were serum starved for 24 hours followed by treatments of P4, 17 hydroxyprogesterone caproate, and medroxyprogesterone 17 acetate (MPA) at 10(-7) mol/L with ethanol as vehicle control; TNF-α at 10, 20, and 50 ng/mL with phosphate-buffered saline (PBS) as control; and H2O2 at 10 and 100 µmol/L with culture media as control for 24, 48, and 72 hours. The messenger RNA (mRNA) and protein expression of PGRMC1 was quantified using polymerase chain reaction and Western blotting, respectively. We found that PGRMC1 protein expression was regulated by MPA, TNF-α, and H2O2 in a dose-dependent manner. This regulation is also specific to the type of cell (amnion, chorion, or decidua). The upregulation of PGRMC1 by MPA might be mediated through glucocorticoid receptor (GR) demonstrated using amnion and chorion cells model with GR knockdown by specific small interfering RNA transfection. The mRNA expression of PGRMC1 was decreased by H2O2 (100 µmol/L) treatment in amnion cells, which might ultimately result in downregulation of PGRMC1 protein as our data demonstrated. None of other treatments changed PGRMC1 mRNA level in these cells. We conclude that these stimuli act as regulatory factors of PGRMC1 in a cell-specific manner.

Progesterone inhibits in vitro fetal membrane weakening.

OBJECTIVE: Inflammation/infection and abruption are leading causes of preterm premature rupture of the membranes. Recently, we identified granulocyte-macrophage colony-stimulating factor (GM-CSF) as a critical mediator of both tumor necrosis factor-α- (TNF; modeling inflammation) and thrombin-induced (modeling abruption) weakening of the fetal membranes. We found that (1) TNF and thrombin both induced GM-CSF in the choriodecidua, (2) blockade of GM-CSF action with neutralizing antibodies inhibited both TNF- and thrombin-induced fetal membrane weakening, and (3) GM-CSF alone induced fetal membrane weakening. GM-CSF is thus part of an overlap of the inflammation and abruption-induced fetal membrane weakening pathways. The effects of progesterone analogs on the pathways by which fetal membranes are weakened have not been investigated. We examined the effects of progesterone, medroxyprogesterone acetate (MPA) and 17α-hydroxyprogesterone (HP) on TNF- and thrombin-induced fetal membrane weakening. STUDY DESIGN: Full-thickness fetal membranes from uncomplicated term repeat cesarean deliveries were mounted in Transwell inserts in Minimum Essential Medium alpha and incubated at 37°C in 5% CO2. The choriodecidua side of the fetal membrane fragments were preincubated with progesterone, MPA, HP, or vehicle for 24 hours. Fetal membranes were then exposed to TNF, thrombin, or GM-CSF on the choriodecidua side for an additional 48 hours. The fetal membrane tissues were then strength tested, and medium from the choriodecidua and amnion compartments was assayed for GM-CSF content. RESULTS: TNF and thrombin both weakened fetal membranes and elevated media GM-CSF levels on the choriodecidua side of the fetal membrane. Pretreatment with progesterone, MPA, or HP inhibited both TNF- and thrombin-induced fetal membrane weakening and also inhibited the induced increase in GM-CSF. GM-CSF decreased fetal membrane rupture strength by 68%, which was inhibited by progestogen pretreatment with a potency order: progesterone

Effect of 17α-hydroxyprogesterone and 17α-hydroxypregnenolone on sperm quality and sperm quantity in male mud spiny lobster (Panulirus polyphagus).

The present study aimed to determine the effect of 17α-hydroxyprogesterone (17α-OHP) and 17α-hydroxypregnenolone (17α-OHPL) on sperm quality and sperm quantity in male mud spiny lobster (Panulirus polyphagus). The mean of sperm quality was increased in 17α-OHP and 17α-OHPL treated hormones. In 17α-OHP injected animals, the mean of sperm quantity of dose 0.01 µg g(-1) b.wt. was increased than 17α-OHPL. Meanwhile, 17α-OHP and 17α-OHPL concentrations were lower when injected with the hormones but 17α-OHP was higher at only day 15 (dose 0.01 and 0.1 µg g(-1) b.wt.). For 17α-OHPL, the hormone was a prohormone in the body of P. polyphagus and only required smaller to increase the sperm quantity. Besides, when the higher dose of 17α-OHPL (0.1 µg g(-1) b.wt.) was used in P. polyphagus, the development of P. polyphagus was inhibited and decreased the sperm quantity and 17α-OHPL concentration in hemolymph was lower. Injection of 17α-OHP in P. polyphagus has increased the sperm quality and quantity for both 17α-OHP dosage of 0.01 and 0.1 µg g(-1) b.wt. However, injection of 17α-OHPL in P. polyphagus has decreased the sperm quantity only, also for both dosage of 0.01 and 0.1 µg g(-1) b.wt. and lower on hormone concentration.

Diosgenone synthesis, anti-malarial activity and QSAR of analogues of this natural product.

Solanum nudum Dunal steroids have been reported as being antimalarial compounds; however, their concentration in plants is low, meaning that the species could be threatened by over-harvesting for this purpose. Swern oxidation was used for hemisynthesis of diosgenone (one of the most active steroidal sapogenin diosgenin compounds). Eighteen structural analogues were prepared; three of them were found to be more active than diosgenone (IC50 27.9 µM vs. 10.1 µM, 2.9 µM and 11.3 µM). The presence of a 4-en-3-one grouping in the A-ring of the compounds seems to be indispensable for antiplasmodial activity; progesterone (having the same functional group in the steroid A-ring) has also displayed antiplasmodial activity. Quantitative correlations between molecular structure and bioactivity were thus explored in diosgenone and several derivatives using well-established 3D-QSAR techniques. The models showed that combining electrostatic (70%) and steric (30%) fields can explain most variance regarding compound activity. Malarial parasitemia in mice became reduced by oral administration of two diosgenone derivatives.

A comparison of the effects of various sex steroids on cholecystokinin- and KCl-induced tension in female guinea pig gallbladder strips.

Estrogen (E) has been shown to have an inhibitory effect on the contractility of gastrointestinal smooth muscle, including the gallbladder. During pregnancy E and progesterone (P) levels are elevated. A biliary stasis may develop during pregnancy that is characterized by an increase in the fasting and residual volumes and by a decrease in emptying capacity. This study investigates the effect of 17ß-estradiol (E2), dihydrotestosterone (DHT), P, 17-hydroxyprogesterone (17-P), and a P metabolite, 20α-hydroxyprogesterone (20-P) on contraction in female guinea pig gallbladder strips. DHT, P, 17-P, 20-P, and E2 each induced a concentration-dependent relaxation of cholecystokinin octapeptide (CCK) induced tension. DHT, E2, and P also induced a concentration-dependent relaxation of KCl-induced tension. When the response to E2 was compared to strips from young female guinea pigs with those taken from guinea pigs in late pregnancy, there was no significant difference in the response to either 50 or 100 µM E2; however, 10 µM E2 caused a significant increase (p<0.05) in the amount of relaxation in strips from pregnant guinea pigs. Treatment of the strips from young guinea pigs with PKA inhibitor 14-22 amide myristolated had no significant effect on the E2-induced relaxation. Treatment of the strips with 2-APB, an inhibitor of IP3 induced Ca(2+) release, produced a significant (p<0.001) increase in the amount of E2-induced relaxation when either CCK or KCl were used. Neither KT5823, a PKG inhibitor, nor L-NMMA, a nitric oxide (NO) synthase inhibitor, had a significant effect on the E2-induced relaxation. Bisindolymaleimide IV and chelerythrine Cl(-), PKC blockers, were used in combination with no significant effect on the amount of CCK-induced tension, but significantly (p<0.01) increased the amount of E2-induced relaxation. When either E2 or P were added to the chambers 3 min prior to either CCK or KCl, a significant decrease (p<0.001) in the amount of tension generated was observed. The inhibition of extracellular Ca(2+) entry mediates both P-induced and E2-induced relaxation of CCK- and KCl-induced tension in female guinea pig gallbladder strips.

Presence of 11-ketotestosterone in pre-differentiated male gonads of Odontesthes bonariensis.

The involvement of androgens during sex differentiation period was investigated in the pejerrey Odontesthes bonariensis, by classic biochemical studies and gonadal histology. We studied in particular whether the enzyme activities involved in 11-oxygenated androgen production were active in a gonadal/peritoneum complex (GPC) of very small larvae exposed to masculinizing temperatures previous to morphological sex differentiation (5 weeks post-hatching). The GPC was incubated with 17-hydroxyprogesterone ((3)H-17P), and the presence of 11-KT as major metabolite in early gonads undergoing masculine pathway after temperature treatment exposure is reported. 11-KT was identified by thin-layer chromatography and high-pressure liquid chromatography. The present results show that 11-KT is produced at very early stages of testis development in pejerrey, being this androgen one of the main mediators of the masculinization induced by temperature treatment at the gonad level.

Progesterone through progesterone receptors affects survival and metabolism of pig sperm.

Progesterone receptors (PR) through interaction with the specific ligand progesterone (PRG), play a central coordinate role in different reproductive events. In this study conventional PR were identified in boar spermatozoa by Western blotting. Immunofluorescence techniques indicate that PR are located at sperm acrosomal region, suggesting a possible role in the oocyte fertilization events. Treatment with 17-hydroxyprogesterone (17-OHP) enhanced viability and induced cholesterol efflux, serine and tyrosine phosphorylation, p-Bcl2, p-Akt that are known hallmarks of capacitation in sperm. The analysis of the triglyceride contents, lipase and acyl-CoA dehydrogenase activities, as well as the G6PDH activity, was conducted so as to address whether there was an increase in energy expenditure via 17-OHP through the PR. Taken together these results, particularly the 17-OHP action on boar sperm lipid and glucose metabolism, give emphasis to the role of PR in sperm physiology within the oviductal environment. Moreover the present study highlights, the effect of PRG via PR on boar sperm survival, renewing the role of this hormone in male reproduction as candidate for boar fertility. Thus the present research contributes to further elucidating the role of progesterone on the physiological regulation of the most relevant spermatozoa functions for a successful fertilization.

Ligand structural motifs can decouple glucocorticoid receptor transcriptional activation from target promoter occupancy.

Glucocorticoid (GC) induction of the tyrosine aminotransferase (TAT) gene by the glucocorticoid receptor (GR) is a classic model used to investigate steroid-regulated gene expression. Classic studies analyzing GC-induction of the TAT gene demonstrated that despite having very high affinity for GR, some steroids cannot induce maximal TAT enzyme activity, but the molecular basis for this phenomenon is unknown. Here, we used RT-PCR and chromatin immunoprecipitation to determine TAT mRNA accumulation and GR recruitment to the TAT promoter (TAT-GRE) in rat hepatoma cells induced by seven GR ligands: dexamethasone (DEX), cortisol (CRT), corticosterone (CCS), 11-deoxycorticosterone (DOC), aldosterone (ALD), progesterone (PRG) and 17-hydroxyprogesterone (17P). As expected, DEX, CRT, CCS and ALD all induced both TAT mRNA and GR recruitment to the TAT-GRE, while PRG and 17P did not. However, while DOC could not induce significant TAT mRNA, it did induce robust GR occupancy of the TAT-GRE. DOC also induced recruitment of the histone acetyltransferase p300 to the TAT-GRE as efficiently as DEX. These DOC-induced effects recapitulated at another GR target gene (sulfonyltransferase 1A1), and DOC also failed to promote the multiple changes in gene expression required for glucocorticoid-dependent 3T3-L1 adipocyte differentiation. Structural simulations and protease sensitivity assays suggest that DOC and DEX induce different conformations in GR. Thus, although steroids that bind GR with high affinity can induce GR and p300 occupancy of target promoters, they may not induce a conformation of GR capable of activating transcription.

Increasing evidence for and regulation of a human placental endogenous digitalis-like factor.

Endogenous digitalis-like factors (EDLFs) appear to be hypertensiogenic and increased in the serum and placenta of women with preeclampsia (PE), a complication of pregnancy. Digibind, an anti-digoxin antibody Fab fragment, reverses in vitro effects of EDLF and in vivo features of PE. We used Digibind in a radioimmunoassay to measure EDLF and compared this to a bio-functional assay of EDLF with good agreement. These methods confirmed that human placenta was a source of EDLF, synthesizing and releasing EDLF into the media of cultured human placental tissue. Ketoconazole, a steroid synthesis inhibitor, and 17-OH progesterone, a possible substrate of steroid synthesis, were shown to inhibit or increase EDLF release respectively, suggesting overlap of synthetic pathways. Abnormalities of PE such as placental hypoxia, increased reactive oxygen species and increased pro-inflammatory cytokines were demonstrated to increase placental EDLF release. These findings strongly support placental production of EDLF with increased release due to features of PE.

Pharmacologic actions of progestins to inhibit cervical ripening and prevent delivery depend on their properties, the route of administration, and the vehicle.

OBJECTIVE: The purpose of this study was to evaluate cervical changes and delivery at term during pregnancy in rats after various progestin treatments. STUDY DESIGN: Pregnant rats were treated by various routes and vehicles with progesterone, 17-alpha-hydroxyprogesterone caproate (17P), R5020, and RU-486. Delivery time was determined and cervical ripening was assessed in vivo by collagen light-induced fluorescence. RESULTS: The cervix is rigid in the progesterone injection, 17P, and vaginal R5020 groups vs controls. Vaginal progesterone had no effect. RU-486 treatment softened the cervix during preterm delivery. Only subcutaneous injected progesterone, R5020 (subcutaneous and vaginal), and topical progesterone in sesame and fish oil inhibits delivery. Delivery is not changed by subcutaneous injection of 17P, vaginal progesterone, oral progesterone, and topical progesterone in Replens (Crinone; Columbia Labs, Livingston, NJ). CONCLUSION: Inhibition of cervical ripening and delivery by progestins depends on many factors that include their properties, the route of administration, and the vehicle. This study suggests reasons that the present treatments for preterm labor are not efficacious.

Effects of 17-hydroxyprogesterone on tumor necrosis factor-alpha-induced hypertension during pregnancy.

BACKGROUND: Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) may be an important link between placental ischemia and hypertension in preeclampsia. We examined the effect of 17-hydroxyprogesterone caproate (17-OHP) on TNF-alpha-stimulated endothelin (ET) production and hypertension during pregnancy. METHODS: TNF-alpha-stimulated ET was examined from endothelial cells cultured in the presence and absence of progesterone. Blood pressure and tissue ET-1 were measured in the following groups of pregnant rats: controls, 17-OHP (3.32 mg/kg), TNF-alpha treated (50 ng/day), TNF-alpha treated+17-OHP. RESULTS: Progesterone abolished TNF-alpha-stimulated ET-1 from endothelial cells. TNF-alpha-induced hypertension was associated with significant increases in renal and placental ET-1. Administration of 17-OHP attenuated TNF-alpha-induced hypertension and decreased renal ET-1. CONCLUSION: Progesterone directly abolished TNF-alpha-stimulated ET-1 and attenuated TNF-alpha-induced hypertension, possibly via suppression of the renal ET-1 system. These data suggest that treatment with progesterone of hypertension associated with elevated cytokines during pregnancy may be worthy of further consideration.

17-Hydroxyprogesterone blunts the hypertensive response associated with reductions in uterine perfusion pressure in pregnant rats.

OBJECTIVE: Reduction in uteroplacental perfusion (RUPP) in pregnant rats is associated with hypertension, elevated cytokines, and activation of the endothelin (ET-1) system. Our objective was to determine whether the antiinflammatory properties of 17-alpha-hydroxyprogesterone caproate (17 OHP) reduce cytokine-stimulated vasoactive pathways that are associated with hypertension in response to placental ischemia. STUDY DESIGN: Mean arterial pressure (MAP), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and renal ET-1 were measured in the following: pregnant controls, pregnant controls plus 17 OHP (6.6 mg/kg), RUPP rats, and RUPP rats plus 17 OHP. RESULTS: MAP increased 29 mm Hg in RUPP rats compared with pregnant controls (P < .001), whereas in RUPP plus 17 OHP rats, MAP increased only 19 mm Hg (P < .05). TNF-alpha and IL-6 increased 2- to 3-fold, respectively, in response to placental ischemia but was normalized in RUPP rats treated with 17 OHP. ET-1 increased 3-fold in RUPP rats but was markedly less in RUPP plus 17 OHP rats. CONCLUSION: 17 OHP blunts hypertension associated with RUPP, possibly via suppression of cytokine-stimulated ET-1 activation.

Effect of progesterone and its synthetic analogues on the activity of mitochondrial permeability transition pore in isolated rat liver mitochondria.

The influence of progesterone and its synthetic analogues on the induction of the Ca(2+)-dependent mitochondrial permeability transition pore (MPTP) has been studied. The novel synthetic analogue of progesterone 17a-acetoxy-3b-butanoyloxy-6-methyl-pregna-4,6-diene-20-on (buterol) was compared with progesterone and medroxyprogesterone acetate (MPA). It was found that progesterone and buterol have opposite effects on the induction of MPTP opening by calcium ions. By contrast to progesterone, which decreased the calcium ion concentration necessary for pore opening, and MPA, which also, although at a lesser extent, activated the pore induction, buterol at a concentration of 20-100 microM blocked the pore opening and increased the calcium retention capacity of mitochondria more than twofold. The action of buterol is specific to the pore since it did not affect the respiration, whereas progesterone completely inhibited NAD-dependent respiration. MPA acted similar to progesterone but less effectively. The inhibitory effect of buterol was eliminated in the presence of carboxyatractyloside, which selectively binds the thiol groups of adenylate translocase and prevents the adenine nucleotide binding. These data indicate that buterol interacts with thiol groups, which explains its inhibitory effect not only on the mitochondrial pore but also on the transport system of xenobiotics in tumor cells in which buterol reduces the multidrug resistance.

Activity lysosomal enzymes in rat skin fibroblasts after treatment with progesterone and new gestagen ABMP.

The effects of a new synthetic gestagen 17alpha-acetoxy-3beta-butanoyloxy-6-methyl-pregna-4,6-dien-20-on (ABMP) and reference drug progesterone on rat skin fibroblasts were evaluated by variations in lysosomal enzyme activity (cathepsin D and beta-glucosidase). Our results suggest that ABMP exhibits lysosomotropic properties, which depended on its concentration and time of treatment. The direct effect of progesterone on lysosomal enzyme activity in skin fibroblasts was compared to the influence of systemic treatment with gestagens on skin lysosomes. The data indicate that local application of gestagen preparations holds much promise for the therapy of skin diseases accompanied by increased proliferation (e.g. psoriasis).

Progesterone, but not 17-alpha-hydroxyprogesterone caproate, inhibits human myometrial contractions.

OBJECTIVE: The aim was to determine whether progesterone (P4) or 17-alpha-hydroxyprogesterone caproate (17P) directly inhibit human uterine contractility in vitro and thereby clarify their mechanisms of action. STUDY DESIGN: Myometrial tissues were suspended in organ chambers and exposed for 2 to 20 hours to varying concentrations of P4 or 17P or solvent. Contractile activity was registered, stored, and analyzed. Dose response curves were then generated for P4 or 17P at various times. RESULTS: P4 significantly inhibited spontaneous contractility dose dependently. The inhibition was not blocked by RU486 but was reversible after washing. Surprisingly, 17P dose dependently stimulated contractility. HPLC and GC-MS methods were used to determine the detectable concentrations of progestins in the baths. CONCLUSION: P4, at concentrations equivalent to those present in the placenta and uterus, inhibit spontaneous myometrial contractility in vitro by nongenomic mechanisms.

Cervical length changes during preterm cervical ripening: effects of 17-alpha-hydroxyprogesterone caproate.

OBJECTIVE: The purpose of this study was to evaluate whether 17-alpha-hydroxyprogesterone caproate (17P) treatment affect changes in cervical length. STUDY DESIGN: Women with singleton pregnancy, between 25 and 33 + 6 weeks of gestation, who were hospitalized for preterm labor were included. Patients with rupture of membranes and/or signs of chorioamnionitis were excluded. Sixty undelivered patients were allocated randomly to either observation or to receive 341 mg of 17P intramuscularly, twice each week until gestational week 36. Cervical length was measured by transvaginal ultrasound scanning at discharge and at day 7 and 21 after discharge. Statistical comparisons were done with analysis of variance and chi-square test. RESULTS: Shortening of the cervix in the observation group (30 cases) was higher than in the 17P group (30 cases) both at day 7 (2.37 +/- 2.0 mm vs 0.83 +/- 1.74 mm; P = .002) and day 21 (4.60 +/- 2.73 mm vs 2.40 +/- 2.46 mm; P = .002). Treatment with 17P was associated with both a reduction in the risk of cervical shortening of > or = 4 mm (odds ratio, 0.18; 95% CI, 0.04-0.66) and in the risk of preterm delivery (odds ratio, 0.15; 95% CI, 0.04-0.58). CONCLUSION: Undelivered patients after preterm labor undergo progressive shortening of the cervix, which is attenuated by 17P treatment.

[Genomic and extragenomic mechanisms of antiglucocorticoid action of gestagens on thymocytes].

Effects of a new synthetic progesterone derivative 17a-acetoxy-3b-butanoyloxy-6-methyl-pregna-4,6-dien-20-one (ABMP) and the reference gestagen preparations on the rat thymus were evaluated by the degree of variation of the intracellular levels of calcium and cAMP, 3H-uridine inclusion into RNA, thymocyte viability, and thymus mass. It is shown that gestagens can produce antiglucocorticoid action on thymocytes, this activity being most pronounced in the case of ABMP.