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Steroid Receptors in the Pregnant Uterus*
Published in Gabor Huszar, The Physiology and Biochemistry of the Uterus in Pregnancy and Labor, 2020
Hideki Sakamoto, Neil MacLusky, Frederick Naftolin
The physiologic role of the “nonreceptor” uterine steroid binding proteins remains uncertain. One possibility is that they may act as intracellular modulators of free steroid concentrations. For example, tissue levels of transcortin are believed to play an important tole in regulating intracellular free glucocorticoid concentrations.42 The various E and P binding components found in the uterus also serve a similar function, i.e., effectively buffering intracellular free steroid levels within physiologically appropriate ranges. In support of this view, Peck et al.43 have reported that after administration of tracer doses of [3H]- estradiol to rats, only 50% of the labeled steroid in the uterus is bound to high affinity receptors.
The Influence of Pituitary-Adrenal Axis on the Immune System
Published in Istvan Berczi, Pituitary Function and Immunity, 2019
Corticosteroid binding globulin (transcortin) did not influence the PHA response of human lymphocytes, if stripped of cortisol.234 When transcortin was added to cortisol, the suppressive effect on the PHA response decreased in proportion to the decrease in the protein free cortisol concentration.235
Pharmacokinetic-Pharmacodynamic Correlations of Corticosteroids
Published in Hartmut Derendorf, Günther Hochhaus, Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Helmut Möllmann, Stefan Baibach, Günther Hochhaus, Jürgen Barth, Hartmut Derendorf
where B is the prednisolone concentration bound to both proteins, CAPT, CAPA, KDT, and KDA the binding capacities and dissociation constants for transcortin and albumin, and CF the free P plasma concentration.10,48 At very low doses (<5 mg) binding to transcortin is maximal at 90 to 95%.45 Doses above approximately 20 mg result in saturation of transcortin with a constant plasma protein binding of about 60%.12,64 In the 5- to 50-mg range higher doses cause a larger Vd and a higher total body clearance,65–68 whereas the terminal half-life of 2 to 4 h remains constant.45,50,58,64,69–70 Since half-life is a function of clearance and Vd, these dose-dependent drug changes compensate each other with respect to t1/2 For P a total body clearance of 5 to 20 l/h (non-protein bound fraction 44 to 63 l/h) and a Vd of 38 to 103 l (105 to 187 l) have been observed.22,45,49,54,72–74 Ultra-high doses cause an unexpected decrease in CLtot, probably due to saturated elimination pathways and/or tissue binding sites.22,65 An additional reason for nonlinear P kinetics is the time and dose-dependent interconversion of P into PR and vice versa, no matter which drug has been administered.47,54,57 For that reason, P/PR ratios are found between 3/1 and 10/1.5,17,75
Hypothalamic-pituitary-adrenal axis activity in post-traumatic stress disorder and cocaine use disorder
Published in Stress, 2020
Natalie A. Hadad, Marek Schwendt, Lori A. Knackstedt
Once CORT is released into the bloodstream, most of it binds immediately with protective carrier proteins, such as cortisol binding globulin (CBG, also known as Transcortin). CBG facilitates CORT transportation throughout the body and prevents it from being metabolized. It should be noted that CBG production is stimulated by estradiol (Feldman et al., 1979), indicating the potential for sex-differences in CORT transport and metabolism. In order for CORT to bind to its target receptor, it must uncouple from its carrier proteins. Thus, CORT that is free, or unbound to binding proteins, is thought to be the biologically active portion of the hormone. Since CORT is small and has a high affinity for lipids, free CORT can passively diffuse into saliva (Baum & Grunberg, 1995). Thus, assaying salivary CORT is a useful and convenient method for measuring free CORT. Whereas assaying salivary and blood CORT allows for the analysis of CORT levels during relatively short intervals (several minutes to 2 h), assaying urinary CORT provides a measure of CORT secretion over a longer period of time (Baum & Grunberg, 1995).
Safety of sugammadex for reversal of neuromuscular block
Published in Expert Opinion on Drug Safety, 2019
GHM Honing, CH Martini, A Bom, M van Velzen, M Niesters, LPHJ Aarts, A Dahan, M Boon
Finally, the model by Zwiers et al. predicted that 34% of etonogestrel (a progestagen metabolite) could be captured by sugammadex, albeit under very conservative model assumptions [65]. Nevertheless, the sugammadex product information advises additional anti-conceptive methods to be used when sugammadex is administered [63]. Depending on the type of hormonal contraceptives, either additional non-hormonal contraceptive methods should be used for 7 days after sugammadex administration, or the contraceptive package leaflet instructions should be followed as if a daily dose was missed [63]. However, the true effects of sugammadex on progestogen levels in vivo remain speculative. Progestogen has a much higher affinity for sex hormone binding globulin (Ka 8.8 megaMol−1) and transcortin (Ka 24 megaMol−1) than for sugammadex (Ka 1.5 megaMol−1) [69]. Indeed, a human study found that the effect of sugammadex 4 mg/kg on serum progesterone or other steroidal hormone levels was not clinically relevant [68].
The effects of combined exposure to noise and heat on human salivary cortisol and blood pressure
Published in International Journal of Occupational Safety and Ergonomics, 2021
Mohammad Javad Jafari, Reza Khosrowabadi, Soheila Khodakarim, Fariba Khodagholi, Farough Mohammadian
Cortisol is a steroid hormone which is released from the hypothalamic–pituitary–adrenal (HPA) axis in response to acute stresses [12]. Koh and Koh [12] along with Levine et al. [13] have shown that the salivary cortisol concentration increases under different physical and psychological stressors. Although blood cortisol levels have been used extensively, e.g., by Aardal-Eriksson et al. [14], to determine stress, this method has certain limits as the process of extracting blood from the veins causes an increase in stress, thereby generating false positive readings. Another flaw in this method is that cortisol levels obtained from serum or plasma only indicate the total cortisol levels and not free or biologically active cortisol. According to Meulenberg et al. [15], certain diseases and the use of certain drugs influence transcortin and albumin, which in turn affect the ratio of total cortisol to free cortisol. Cortisol is metabolized in the liver, of which 75% is released by the kidneys as free cortisol; this depends on the function of the glomerulus and the Henle loop. According to Yehuda et al. [16], cortisol readings from urine depend on suitable methods of extraction over the past 24 h while urine cortisol levels do not correlate well with free cortisol levels in the bloodstream. Considering the aforementioned flaws, the use of salivary cortisol levels is more suitable in contemporary studies. Kaufam and Lamster [17] as well as Clements and Parker [18] also believe that salivary cortisol correlates well with free cortisol levels in the blood (