Likewise, a novel isoform of ERβ, termed ERβ2, containing an in-frame insertion of an exon of 54 nucleotides, resulting in an insertion of 18 amino acids in the LBD, was recently identified first by screening rat prostate cDNA library, and is also expressed in human cell lines. 43 ERβ2 binds E 2 with lower affinity (Kd = 8 nM) than ERβ1 (Kd = 1 nM). At least 10 splice variants of ERβ have been identified. 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55
The secretion of hypothalamic, pituitary, and target tissue hormones is under tight regulatory control by a series of feedback and feed- forward loops. This complexity can be demonstrated using the growth hormone (GH) regulatory system as an example. The stimulatory substance growth hormone releasing hormone (GHRH) and the inhibitory substance somatostatin (SS) both products of the hypothalamus, control pituitary GH secretion. Somatostatin is also called growth hormone-inhibiting hormone (GHIH). Under the influence of GHRH, growth hormone is released into the systemic circulation, causing the target tissue to secrete insulin-like growth factor-1, IGF-1. Growth hormone also has other more direct metabolic effects; it is both hyperglycemic and lipolytic. The principal source of systemic IGF-1 is the liver, although most other tissues secrete and contribute to systemic IGF-1. Liver IGF-1 is considered to be the principal regulator of tissue growth. In particular, the IGF-1 secreted by the liver is believed to synchronize growth throughout the body, resulting in a homeostatic balance of tissue size and mass. IGF-1 secreted by peripheral tissues is generally considered to be autocrine or paracrine in its biological action.
Retinoids are polyisoprenoid lipids derived from retinol (vitamin A). They perform multiple regulatory functions in diverse cellular processes. Retinoids regulate cellular proliferation, differentiation , and death, and they have numerous clinical applications. Their diverse effects reflect, at least in part, the multiplicity of retinoid derivatives, the existence of two different classes of receptors that form heterodimers, and differences in their cis-acting regulatory sites on DNA . During development retinoids act as local mediators of cell-cell interaction. For instance, during the formation of motor neurons in the chick, one class of motor neurons generates a retinoid signal which regulates the number and type of neighboring motoneurons.