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Steroid hormone bioavailability is controlled by the lymphatic system.

ABSTRACT: The steroid hormone progesterone accounts for immune tolerance in pregnancy. Enhanced progesterone metabolism to 6α-OH-pregnanolone occurs in complicated pregnancies such as in preeclampsia with preterm delivery or intrauterine growth restriction, and in cancer. As lymphatic endothelial cells (LECs) promote tumor immunity, we hypothesized that human LECs modify progesterone bioavailability. Primary human LECs and mice lymph nodes were incubated with progesterone and progesterone metabolism was analyzed by thin layer chromatography and liquid chromatography-mass spectrometry. Expression of steroidogenic enzymes, down-stream signal and steroid hormone receptors was assessed by Real-time PCR. The placental cell line HTR-8/SV neo was used as reference. The impact of the progesterone metabolites of interest was investigated on the immune system by fluorescence-activated cell sorting analysis. LECs metabolize progesterone to 6α-OH-pregnanolone and reactivate progesterone from a precursor. LECs highly express 17β-hydroxysteroid dehydrogenase 2 and are therefore antiandrogenic and antiestrogenic. LECs express several steroid hormone receptors and PIBF1. Progesterone and its metabolites reduced TNF-α and IFN-γ production in CD4+ and CD8+ T cells. LECs modify progesterone bioavailability and are a target of steroid hormones. Given the global area represented by LECs, they might have a critical immunomodulatory control in pregnancy and cancer.

SUBMITTER: Klossner R

PROVIDER: S-EPMC8102502 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Essentials Endogenous hormone levels' influence on hemostatic factor levels is not fully characterized. We tested for associations of endogenous hormone with hemostatic factor levels in postmenopause. Estrone levels were inversely associated with the natural anticoagulant, protein S antigen. Dehydroepiandrosterone sulfate levels were inversely associated with thrombin generation.SummaryBackground Oral use of exogenous estrogen/progestin alters hemostatic factor levels. The influence of endogenous hormones on these levels is incompletely characterized. Objectives Our study aimed to test whether, among postmenopausal women, high levels of estradiol (E2), estrone (E1), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), and androstenedione, and low levels of sex hormone-binding globulin (SHBG), are positively associated with measures of thrombin generation (TG), a normalized activated protein C sensitivity ratio (nAPCsr), and factor VII activity (FVIIc), and negatively associated with antithrombin activity (ATc) and total protein S antigen (PSAg). Methods This Heart and Vascular Health study cross-sectional analysis included 131 postmenopausal women without a prior venous thrombosis who were not currently using hormone therapy. Adjusted mean differences in TG, nAPCsr, FVIIc, ATc and PSAg levels associated with differences in hormone levels were estimated using multiple linear regression. We measured E2, E1, total T, DHEAS, DHEA and androstenedione levels by mass spectrometry, SHBG levels by immunoassay, and calculated the level of free T. Results One picogram per milliliter higher E1 levels were associated with 0.24% lower PSAg levels (95% Confidence Interval [CI]: -0.35, -0.12) and 1 μg mL-1 higher DHEAS levels were associated with 40.8 nm lower TG peak values (95% CI: -59.5, -22.2) and 140.7 nm×min lower TG endogenous thrombin potential (ETP) (95% CI: -212.1, -69.4). After multiple comparisons correction, there was no evidence for other associations. Conclusions As hypothesized, higher E1 levels were associated with lower levels of the natural anticoagulant PSAg. Contrary to hypotheses, higher DHEAS levels were associated with differences in TG peak and ETP that suggest less generation of thrombin.

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Steroid hormone bioavailability is controlled by the lymphatic system.

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