Progesterone transport

Because of the rapid and nonlinear kinetics of testosterone and progesterone transport, Pe is calculated by Eq. (7) in the form... 

Transport of cortisol, corticosterone and progesterone Transport of progesterone Transport of iodotharonins... 

Pregnenolone is transported from the mitochondria to the ER, where a hydroxyl oxidation and migration of the double bond yield progesterone. Pregnenolone synthesis in the adrenal cortex is activated by adrenocorticotropic hormone (ACTH), a peptide of 39 amino acid residues secreted by the anterior pituitary gland. 

The summary of Pe values for the steroids as a function of stirring rates is found in Table 11 and their correlations with log PC (n-octanol-water) in Figure 20. The transport kinetics of the relatively hydrophilic hydrocortisone and dexa-methasone are controlled by passive diffusion across the cell monolayer. On the other hand, the Pe values of testosterone and progesterone are highly dependent on stirring rate. The results for testosterone are used to obtain the relationships between the effective permeability coefficients of the ABL on the donor and receiver sides and the stirring rate, using the linear expression (see Eq. (69)]... 

A comparison of the transport quality (Fig. 20.11(B)) with the rate of P-gp-ATPase activation (see Fig. 20.9) as a function of the H-bond energy (EUh) shows that compounds inducing a high rate of ATP hydrolysis (e.g., progesterone) can have a low substrate quality , and vice versa (e.g., cyclosporin). 

A.B. Shapiro, K. Fox, P. Lam, and V. Ling. Stimulation of P-glycoprotein-mediated drug transport by prazosin and progesterone. Evidence for a third drugbinding site. Eur J Biochem. 259 841-850 (1999). 

Fig. 9.8 Examples of rule-of-three compliant molecules that have biological activity better than 10 nM. Under each molecule, the following information is included molecule name, MW, ClogP, the biological activity type, value and target. Target names are as follows D3 and D4 - dopaminergic receptor types 2 and 3 AChE and BChE - acetyl- and butyryl-choline esterases PRa and PRb - progesterone receptor types A and B H] and H3, histamine receptor types 1 and 3 5-HT2a, 5-HT2b, 5-HT2c, 5-HT3, 5-HT4 - serotonin receptor subtypes 2A, 2B, 2C, and types 3 and 4 DAT, NET, 5-HTT - dopamine, norepinephrine and serotonin transporter proteins /X], /x.2, S, ki, ks - opioid receptor types mu-1, mu-2, delta, kappa-1 and kappa-3 5a-Rl and 5o -R2 - 5-alpha-reductase isozymes 1 and 2 Flt-1-fms-like tyrosine kinase receptor.

It was shown that liposomes, due to their structure, have a retarding effect on the incorporated drug release. In early studies, Knepp et al. reported that progesterone release from agarose gel was faster than from liposomes embedded in the gel [29]. This retarding release behavior from liposomes was further confirmed by a lower drug transport rate as compared to the gel measured across hairless mouse skin [30], Another study by Foldvari et al. [8] examined the... 

It is important to note that P-gp inhibition by a compound for the efflux of any of these ligands does not directly correlate with the ability of P-gp to efflux the compound of interest (177). Such is the case with paclitaxel, which is considered to be an excellent P-gp substrate but a poor inhibitor as determined by the dye-efflux method. The converse is seen with progesterone, which is a good inhibitor of P-gp-mediated efflux and yet is a poor substrate. It is important to note that P-gp inhibition can occur in several ways—competitively, non-competitively, and via inhibition of ATP hydrolysis at the Walker A and B motifs (271). Furthermore, the false negatives due to poor permeability noted for transport assays can also produce false negatives in these interaction assays. 

---