Progesterone membrane effects

Progesterone produces direct membrane effects [16]. These include actions that promote maturation of spermatozoa as well as oocytes and facilitation of the release of neurotransmitters such as dopamine and LH-releasing hormone (LHRH) (Fig. 52-7). Membrane actions of progesterone also activate oxytocin receptors in the hypothalamus in a way that enables oxytocin to turn on sexual behavior in the estrogen-primed female rat [3],... 

The hormone-releasing devices have a closer resemblance to standard methods of sustained release because they involve the release of a steroid compound by diffusion [198,199]. The Progestasert, a reservoir system, is shown in Fig. 16. Progesterone, the active ingredient, is dispersed in the inner reservoir, surrounded by an ethylene/vinyl acetate copolymer membrane. The release of progesterone from this system is maintained almost constant for 1 year. The effects of release are local, with none of the systematic side effects observed with orally administered contraceptives [200-207]. 

Two other, faster-acting mechanisms produce some of the effects of steroids. Progesterone triggers a rapid drop in [cAMP], mediated by a plasma membrane receptor, and binding of progesterone to the classic soluble steroid receptor activates a MAPK cascade. 

The presence of the term y) makes the permeability coefficient a function of the solvent used as the liquid phase. Some experimental data illustrating this effect are shown in Figure 2.7 [11], which is a plot of the product of the progesterone flux and the membrane thickness, 7, against the concentration difference across the membrane, (cio — cif ). From Equation (2.28), the slope of this line is the permeability, P]. Three sets of dialysis permeation experiments are reported, in which the solvent used to dissolve the progesterone is water, silicone oil and poly(ethylene glycol) MW 600 (PEG 600), respectively. The permeability calculated from these plots varies from 9.5 x 10 7 cm2/s for water to 6.5 x 10 10 cm2/s for PEG 600. This difference reflects the activity term yj/ in Equation (2.28). However, when the driving force across the membrane is... 

Steroid Receptors. Steroid receptors such as estrogen, progesterone, and androgen receptors are overexpressed in breast, ovarian, and prostate cancers. Estrogen and progesterone receptors are present in about 65% of human breast cancers. The presence or absence of these receptors in cases of breast carcinoma assists the determination of the therapeutic strategy (hormonal or chemical) that is likely to be effective. The successful Tc complex must cross the membrane lipid bilayer of the cell, and thus, the size and lipophilicity of the complex must be balanced with receptorbinding affinity. 

In animals, estrogen has been shown to influence the effect of antidepressants on the brain. Wilson showed that estradiol increased the binding of imipramine to the uptake of serotonin at membrane sites. Estrone had no effect, but the addition of progesterone to low doses of estrogen increased this effect. In all, the greatest effect seen was about a 20% enhancement of imipramine binding (Wilson et al., 1986). 

But how do these ovarian and testicular hormones exert their effects All cells that interact with these steroid hormones have receptors for them within the cytoplasm. The presence of oestrogen receptors was first demonstrated by Jensen and Jacobsen in 1962. The hormones pass through the cell membrane and then encounter receptors that are specific for each of the classes of hormones the oestrogens, androgens, progesterone and glucocorticoids... 

Certain effects of progesterone, such as increased Ca mobilization in sperm, occur within minutes and reflect nongenomic mechanisms involving membrane-bound PRs that are not derived from the gene encoding PRffPR ... 

In the phase of estrus when the levels of estrogens and progesterone are the highest, the observed uterine response is a sustained contraction. A reduction of the uterotonic activity is observed as hormone levels decrease, which is linked to changes on membrane receptor population for some neurotransmitters. The effect of GA on anestrus is a clear relaxation specially when estrogen levels are the lowest (diestrus phase) "Fig. (4)" [32]. 

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