Human Biochemistry Volume 2 - Murray R. 1993

Biochemistry of Intra- and Intercellular Communication
Sex Hormones
Mechanism of Action of Ovarian Hormones

The primary effects of estrogens and progestins stem from their ability to bind to intracellular receptors. The resulting hormone-receptor complex interacts with specific regions of Chromatin or DNA, altering the METABOLISM/31.html">Transcription rate of specific genes. Most data on this matter were obtained by studying how estradiol and progesterone stimulate the transcription of avian egg-white protein genes (specifically, the Ovalbumin and conalbumin genes). The exact mechanism of hormonal Gene transcription activation is currently under intensive investigation.

Estrogen Receptors

The Amino Acid Sequence of human and chicken estrogen-binding receptor Proteins was determined by analyzing The nucleotide sequence of full-length cDNA molecules. Three highly conserved regions were identified in each of these molecules, with the second and third corresponding to the DNA- and hormone-binding domains of the receptors. The hormone-binding domain exhibits strong hydrophobic properties, while the DNA-binding domain is rich in Cysteine and basic amino acid residues. These two estrogen receptor domains are conserved in glucocorticoid, progesterone, and calcitriol receptors, as well as in the v-erb-A gene product. All DNA-binding proteins may derive from a common ancestral gene.

Notable Features

Several key features deserve attention, as they may relate to the MECHANISM OF ACTION of Other Hormones: 1) sex Hormone Receptors are capable of cross-reactivity. Progesterone, for instance, binds to androgen receptors and thus acts as a weak androgen. Certain androgens bind to estrogen receptors and mimic their effects in the Uterus; 2) estrogen exposure increases the concentration of both estrogen and progesterone receptors; 3) progesterone appears to accelerate the turnover rate of its own receptors; 4) so-called weak estrogens, such as estriol, behave as potent estrogens when administered frequently.

Receptor-Independent Actions of Sex Hormones

Are all effects of Steroid Hormones mediated by receptors? This question has long been debated. Recent evidence suggests that certain effects may be receptor-independent and presumably do not involve nuclear processes.

A. Estrogens. Estrogens can act independently of their receptors. The relative stimulation of uterine Blood flow by various estrogens does not correlate with their receptor-binding affinity, nor does this effect require RNA Synthesis. This may reflect a direct hormonal influence on histamine release and prostaglandin production. Although less definitively proven than the membrane effects of progesterone, direct action may constitute an important component of the Physiological effects of estrogens.

B. Progestins. The interaction of progesterone with The Cell membrane of amphibian oocytes triggers a hormone- and time-dependent increase in intracellular calcium concentration, which in turn stimulates the Synthesis of specific cytoplasmic proteins presumably involved in oocyte maturation; transferring these proteins to other immature oocytes induces maturation. This effect is also observed in enucleated oocytes (indicating that gene transcription is not involved). Conversely, microinjection of progesterone directly into the egg produces no effect. This is likely not an isolated example.