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DNA synthesis

20-30 hr

Acceleration of cell division

" Modified from Fig. 1 of Katzenellenbogen, B. S., and Gorski, J. (1975). Estrogen action on syntheses of macromolecules in target cells. In "Biochemical Actions of Hormones" (G. Litwack, ed.), Vol. 3, p. 187. Academic Press, New York.

" Modified from Fig. 1 of Katzenellenbogen, B. S., and Gorski, J. (1975). Estrogen action on syntheses of macromolecules in target cells. In "Biochemical Actions of Hormones" (G. Litwack, ed.), Vol. 3, p. 187. Academic Press, New York.

4. Progesterone a. Background

In contrast to estradiol, the biological actions of progesterone are largely restricted to the female reproductive tract and mammary tissue. Table 13-6 tabulates many of the known biological actions of progesterone. Receptors for progesterone have been found in the uterus, mammary tissue, placenta, and anterior pituitary.

b. Progesterone Receptors

The human progesterone receptor (PR) gene and cDNA have been cloned and evaluated. While there is only one gene, two distinct mRNA species generate two functionally different protein receptor forms, A and B (see Figure 13-16). The two mRNA species are transcribed from the single gene under the control of separate A and B promoters, both of which are known to be activated by estradiol and the ER.

The human PRB protein consists of 933 amino acids (115-kDa molecular mass), while the PRA protein consists of 768 amino acids (82 kDa). The two PR proteins are identical except that PRA lacks the first 165 amino acids present on the amino terminus of PRB.

Both the A and B forms of the progesterone receptor are functional, like all steroid receptors, as a transcriptional regulatory protein. The general model of the ER regulation of gene transcription shown in Figure 1315 is also applicable to the PR. The consensus sequence of the hormone response element (HRE) for the PR is similar to that of the glucocorticoid HRE (see Table 110) and is shown here: AGAACAnnnTGTTCT.

There is emerging evidence that, although both the PRa and PRB are able to bind ligands and interact with the HRE, they are functionally different. On the basis of transfection studies, the two receptor forms were found to have both promoter-specific and cell-specific differences. This suggests that the cellular responsiveness to progesterone may be modulated via alteration in the ratio of tissue expression of PRA and PRB in target cells.

The presence of PR in breast tumors is generally indicative of a possible responsiveness to endocrine treatments. Intriguingly, it has been found that a significant proportion of PR-positive breast tumors expressed atypically low amounts of PRB; the significance of this observation remains to be elucidated.

B. Mechanisms of Progesterone and

Estrogen Receptor Action (As Exemplified by the Chick Oviduct System)

One system that has contributed extensively to our current understanding of the mode of action of steroid hormones is the chick oviduct. W. Schr├Ąder, B. O'Mal-

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Cure Tennis Elbow Without Surgery

Cure Tennis Elbow Without Surgery

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