Transcortin: A Corticosteroid-Binding Protein of Plasma. X. Cortisol and Progesterone Interplay and Unbound Levels of These Steroids in Pregnancy

Rosenthal, Hannah E.; Slaunwhite, W. Roy; Sandberg, Avery A.

doi:10.1210/jcem-29-3-352

Cited by 207 publications

(71 citation statements)

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“…A crossreaction on the CBG occurs principally with corticosterone (100%), progesteron (20-40%) and cortisone (10%). While most steroids except cortisol and cortisone are quantatively insignificant, progesteron raises during pregnancy and at term it may displace 30% of cortisone found to CBG [15]. Therefore, our values are inpart considerably higher than cortisol concentrations reported by other authors.…”

Section: Methodscontrasting

confidence: 66%

Maternal and fetal plasma levels of free corticosteroids during normal delivery

Schmid¹,

Briner²

1975

Journal of Perinatal Medicine

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Section: Methodscontrasting

confidence: 66%

Maternal and fetal plasma levels of free corticosteroids during normal delivery

Schmid¹,

Briner²

1975

Journal of Perinatal Medicine

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“…3A). DOC concentrations reach 0.2 -0.3 nmol/l during the follicular and luteal phase, but they increase up to 1.8 nmol/l during pregnancy (16,17), which could be a compensatory effect for the increasing concentrations of progesterone.…”

Section: Doc and Hmrmentioning

confidence: 93%

“…During the luteal phase of the menstrual cycle, progesterone plasma concentrations range between 30 and 110 nmol/l. During pregnancy the concentrations rise steadily until they peak at the end of the third trimester in the range 320 -700 nmol/l (16,17). In contrast, plasma aldosterone increases only slightly during the luteal phase and late pregnancy (0.6 and 5.8 nmol/l respectively) (18).…”

Section: Introductionmentioning

confidence: 99%

Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor

Quinkler

Meyer

Bumke-Vogt

et al. 2002

European Journal of Endocrinology

117

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Objective: Progesterone binds to the human mineralocorticoid receptor (hMR) with nearly the same affinity as do aldosterone and cortisol, but confers only low agonistic activity. It is still unclear how aldosterone can act as a mineralocorticoid in situations with high progesterone concentrations, e.g. pregnancy. One mechanism could be conversion of progesterone to inactive compounds in hMR target tissues. Design: We analyzed the agonist and antagonist activities of 16 progesterone metabolites by their binding characteristics for hMR as well as functional studies assessing transactivation. Methods: We studied binding affinity using hMR expressed in a T7-coupled rabbit reticulocyte lysate system. We used co-transfection of an hMR expression vector together with a luciferase reporter gene in CV-1 cells to investigate agonistic and antagonistic properties. Results: Progesterone and 11b-OH-progesterone (11b-OH-P) showed a slightly higher binding affinity than cortisol, deoxycorticosterone and aldosterone. 20a-dihydro(DH)-P, 5a-DH-P and 17a-OH-P had a 3-to 10-fold lower binding potency. All other progesterone metabolites showed a weak affinity for hMR. 20a-DH-P exhibited the strongest agonistic potency among the metabolites tested, reaching 11.5% of aldosterone transactivation. The agonistic activity of 11b-OH-P, 11a-OH-P and 17a-OH-P was 9, 5.1 and 4.1% respectively. At a concentration of 100 nmol/l, progesterone, 17a-OH-P and 20a-DH-P inhibit nearly 75, 40 and 35% of the transactivation by aldosterone respectively. All other progesterone metabolites tested demonstrate weaker affinity, and agonistic and antagonistic potency. Conclusions: The binding affinity for hMR and the agonistic and antagonistic activity diminish with increasing reduction of the progesterone molecule at C20, C17 and at ring A. We assume that progesterone metabolism to these compounds is a possible protective mechanism for hMR. 17a-OH-P is a strong hMR antagonist and could exacerbate mineralocorticoid deficiency in patients with congenital adrenal hyperplasia.

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“…Rat serum (67%) only inhibited the transport of these four hormones, 0, 13, 12, and 69%, respectively, reflecting the absence of a sex hormone-binding globuDr. Pardridge is the recipient of Clinical Investigator Award Receivedfor publication 22 December 1978 and in revised form 16 March 1979. lin in rat plasma. However, neonatal rat serum (67%) inhibited progesterone, testosterone, and estradiol transport 0, 0, and 91%, respectively, consistent with the presence ofan estradiol-binding protein in neonatal rat serum.…”

mentioning

confidence: 99%

Transport of Steroid Hormones through the Rat Blood-Brain Barrier

Pardridge¹,

Mietus²

1979

J. Clin. Invest.

391

128

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A B S T R A C T These studies were undertaken to investigate (a) the permeability properties of the bloodbrain barrier (BBB) to the major gonadal and adrenal steroid hormones, and (b) the role of the binding proteins of plasyna (albumin and specific globulins) in the regulation of BBB steroid hormone transport.The testosterone, 85+1%; estradiol, 83+3%; corticosterone, 39±2%; aldosterone, 3.5±0.8%; and cortisol, 1.4±0.3%. The selective permeability of the BBB was inversely related to the number of hydrogen bonds each steroid formed in aqueous solution and directly related to the respective I-octanol/Ringer's partition coefficient.When the bolus injection was 67% human serum, >95% of the labeled steroid was bound as determined by equilibrium dialysis. However, the influx of the steroids through the BBB was inhibited by human serum to a much less extent than would be expected if only the free (dialyzable) hormone was transported; progesterone, estradiol, testosterone, and corticosterone transport was inhibited 18, 47, 70, and 85% respectively, or in proportion to the steroid binding to plasma globulins. Rat serum (67%) only inhibited the transport of these four hormones, 0, 13, 12, and 69%, respectively, reflecting the absence of a sex hormone-binding globu- KD(app), to the in vitro KD was: >200 for progesterone, >200 for testosterone, 120 for estradiol, and 7.7 for corticosterone. Assuming the steady-state condition, the KD(app)/KD was found to be proportional to the BBB permeability for each steroid.These data demonstrate (a) the selective permeability properties ofthe BBB to the major steroid hormones is proportional to the tendency ofthe steroid to partition in a polar lipid phase and is inversely related to the number of hydrogen bond-forming functional groups on the steroid nucleus; (b) the presence of albumin in serum may bind considerable quantities of steroid hormone, but exerts little inhibitory effects on the transport of steroids into brain, whereas globulin-bound hormone does not appear to be transported into brain to a significant extent. Therefore, the hormone fraction in plasma that is available for transport into brain is not restricted to the free (dialyzable) fraction, but includes the larger albumin-bound moiety.

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Transcortin: A Corticosteroid-Binding Protein of Plasma. X. Cortisol and Progesterone Interplay and Unbound Levels of These Steroids in Pregnancy

Cited by 207 publications

References 0 publications

Maternal and fetal plasma levels of free corticosteroids during normal delivery

Maternal and fetal plasma levels of free corticosteroids during normal delivery

Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor

Transport of Steroid Hormones through the Rat Blood-Brain Barrier

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