Hormones that Affect Gene Activity

Lipid-soluble hormones act usually by gene activation/deactivation. Examples of these hormones include steroids, thyroid hormone, and vitamin A (retinoic acid). The hormones are transported through the circulation in association with a hormone-binding protein and are soluble in the plasma membrane of the cell. Their receptors are intracellular, and they act on gene transcription (the synthesis of messenger RNA) rather than at the protein level. Thus, they act more slowly than do the soluble hormones, on the scale of days rather than minutes. 

The sequence of events in gene activation contains several steps. First, in the hormone-free state, the unoccupied receptor is bound to the nuclear membrane and loosely to chromatin. (Chromatin is the DNA-protein complex of chromosomes.) After the hormone binds the receptor, it changes its location. The receptor-hormone complex binds DNA tightly and thereby activates or inactivates the synthesis of mRNA from these genes. The specificity of these receptors lies in two properties their ability to bind different hormones and their ability to bind different DNA sequences. 

the possibility of cross-talk exists between metabolic and genetic events. Thus, for example, steroids may bind to one receptor, which itself will interact with other proteins. Some of these proteins may be phosphorylated by kinases that respond to the presence of cAMP or a Ca2+ ion. 

The regions of the secondary structure do not have to form between sequences that are close together. For example, base-pairing between the sequences at the 5 and 3 ends forms the acceptor stem of transfer RNA. The tertiary structure of a nucleic acid refers to the three-dimensional arrangement of the nucleic acid—that is, the arrangement of the molecule in space, as in the tertiary structure of IRNA. 

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Water-soluble hormones must transmit signals to affect metabolism and gene ejcpression without themselves entering the cytoplasm. They often do so via second messenger systems that, in turn, activate protein kinases. 

In vivo studies in animals suggest that endosulfan may disrupt normal reproductive hormone levels in male animals, but that it is not an endocrine disrupter in females. Persistent depressed testicular testosterone was seen in male rats after intermediate duration oral exposures to endosulfan. In ovariectomized female rats, orally administered endosulfan did not induce normal development of female reproductive tissues, and in female mice and immature female rats, acute parenteral exposure to endosulfan did not affect several endocrine-related end points. In vitro studies have evaluated endosulfan for estrogen receptor (ER) and cytosolic protein binding affinity, ER-mediated reporter gene expression, estrogenic induction of cell proliferation, and alteration of relative abundance of active estradiol metabolites. Overall, in vitro evidence in favor of endosulfan estrogenicity indicates relatively weak potency compared to 17[3-estradiol. Apparently contradictory results were reported in different... 

Hormonal actions on target neurons are classified in terms of cellular mechanisms of action. Hormones act either via cell-surface or intracellular receptors. Peptide hormones and amino-acid derivatives, such as epinephrine, act on cell-surface receptors that do such things as open ion-channels, cause rapid electrical responses and facilitate exocytosis of hormones or neurotransmitters. Alternatively, they activate second-messenger systems at the cell membrane, such as those involving cAMP, Ca2+/ calmodulin or phosphoinositides (see Chs 20 and 24), which leads to phosphorylation of proteins inside various parts of the target cell (Fig. 52-2A). Steroid hormones and thyroid hormone, on the other hand, act on intracellular receptors in cell nuclei to regulate gene expression and protein synthesis (Fig. 52-2B). Steroid hormones can also affect cell-surface events via receptors at or near the cell surface. 

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