Testosterone transport

Measurements of Pe in fixed-pH solutions but at various different stirring speeds need to be made. The double-reciprocal analysis, HPe versus 1/v , for Caco-2 permeability measurements in the Transwell (Corning Costar) system produced a linear plot for x- 0.8 [514]. The intercept yields the membrane permeability for the particular pH value in the study the slope determines the k constant. From the analysis of testosterone transport, for the stirring speed of 25 rpm (planar rotating shaker), the thickness of each UWL (assuming symmetric geometry) was calculated to be 465 pm at 150 rpm, haq= 110 pm [514], Karlsson and Artursson [512] found x = 1.0 to best represent their stirring-based analysis of the UWL permeability. 

Hamada A, Sissung T, Price DK, Danesi R, Chau CH, Sharifi N, Venzon D, Maeda K, Nagao K, Sparreboom A, Mitsuya H, Dahut WL, Figg WD (2008) Effect of SLC01B3 haplotype on testosterone transport and clinical outcome in Caucasian patients with androgen-independent prostatic cancer. Clin Cancer Res 14 3312-3318... 

Hemopexin (binds heme) Retinol-binding protein (binds retinol) Sex hormone-binding globulin (binds testosterone, estradiol) Thyroid-binding globulin (binds T4, T3) Transferrin (transport iron)... 

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

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)]... 

Buur A, N Mprk. (1992). Metabolism of testosterone during in vitro transport across Caco-2 cell monolayers Evidence for beta-hydroxysteroid dehydrogenase activity in differentiated Caco-2 cells. Pharm Res 9 1290-1294. 

Fig. 15.2. Physicochemical molecular descriptors affect the transport route utilised across the intestinal epithelium. To passively diffuse through the membrane (1), the compound (here illustrated with testosterone) should preferably be small, with a molecular weight <500 Da, as well as uncharged and fairly lipophilic. However, compounds that are too lipophilic can stick to the membrane and will not pass through the cells. The paracellular route (2), here exemplified with mannitol, is mainly utilised by smaller (Mw < 200 Da)...

Transferrin 8-9 Binds iron in plasma and transports iron to bone Iron deficiency, pregnancy, hypoxia, chronic blood loss, estrogens Chronic infection, cirrhosis, burns, enteropathies, nephrotic syndrome, cortisone, testosterone... 

Only 2% of total plasma testosterone is present in the active unbound state that penetrates the prostate cell, where it is converted to DHT by 5 a-reductase. DHT subsequently binds with a cytoplasmic receptor and is transported to the cell nucleus where transcription and translation of stored genetic material occur. 

Prenatal and postnatal exposures to fenvalerate reduced prostate and seminal vesicle weights and plasma testosterone levels in male rats [55], A chronic study showed no adverse effects on reproductive tissues at a high dose level of 1,000 ppm [142]. In vivo and in vitro studies with rats and mice suggested that fenvalerate may affect male and female reproduction, possibly due to calcium transport alteration [143-146], One paper reported that fenvalerate affected human sperm count and sperm motility of male workers who were exposed to fenvalerate in a pesticide factory [147]. 

Transport of testosterone and estradiol Transport of vitamin B12 Complement activation... 

Testosterone is transported in the blood bound to transport proteins, the most important of which are albumin (a non-specific carrier) and testosterone-oestradiol binding globulin (TEBG), a 40kDa polypeptide which binds testosterone and oestrogens with high affinity. 

Sertoli cells, in the seminiferous tubule wall, are known to be important in spermatogenesis, in part through their synthesis of an androgen-binding protein (ABP). ABP, when secreted into the lumen of the seminiferous tubules, selectively binds testosterone of Leydig cell origin and serves as a hormone reservoir and transport protein for the androgen. 

This behaviour was observed with testosteroxy-trimethylsilane (lb) in biological experiments33. The androgenic and myotropic activities of testosterone (la) and its silyl derivative lb were estimated by a routine assay (21-day-old castrated male rats s.c. injection once a day for 7 days autopsies the day after the last injection). The silyl compound lb was more active than testosterone itself. This observation may reflect rapid transport of the silicon compound across the lipid barrier and rapid cleavage to testosterone. 

Shackleford, D.M., et al. 2003. Contribution of lymphatically transported testosterone undecanoate to the systemic exposure of testosterone after oral administration of two andriol formulations in conscious lymph duct-cannulated dogs. J Pharmacol Exp Ther 306 925. 

FSH, for example, increases the expression of a polypeptide known as androgen-binding protein (ABP). ABP helps concentrate testosterone within the seminiferous tubules and helps transport testosterone to the epididymis.39 FSH may also affect Leydig cell function indirectly by increasing the production of other chemical messengers from the Sertoli cells that enhance differentiation and function of Leydig cells.146 147... 

Cimetidine (for treatment of peptic ulcers) competes with dihydrotestosterone for receptors in the testis and accessory sex glands. The more common sequelae are low sperm count and gynacomastia. Epidemiological evidence has shown that occupation exposure to oral contraceptives can induce gynacomastia in exposed males. Diethylstilbestrol (DES) antagonizes the activity of fetal testosterone. In the male offspring, testicular hypoplasia, abnormal semen parameters, and infertility result. Ketoconazole has be shown to be transported to the seminal fluid and to immobilize the sperm. 

Figure 3 Correlation between the fraction absorbed and the membrane permeability in Caco-2 cells. Papp represents the membrane permeability of following 20 compounds, and was obtained by measuring the transcellular transport from the apical-to-basal side in Caco-2 cells. The fraction absorbed was obtained from literature. A amoxicillin, B antipyrine, C atenolol, D caffein, E cephalexin, F cyclosporin A, G enalaprilate, H L-glutamine, I hydrocortisone, J inulin, K D-mannitol, L metoprolol, M L-phenylalanine, N PEG-400, O PEG-4000, P propranolol, Q sucrose, R taurocholate, S terbutaline, T testosterone. Source From Ref. 37.

Subsequent research demonstrated a coordinated, dose-dependent reduction in expression of key genes and proteins involved in cholesterol transport and steroidogenesis and a corresponding reduction in testosterone in the fetal testes (Lehmann et al.,... 

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