Insulin-like growth factor 2

Insulin-like growth factor 2 (IGF-2) is one of three protein is_associated_with::hormones that share structural similarity to is_associated_with::insulin. The MeSH definition reads: "A well-characterized neutral is_associated_with::peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on is_associated_with::somatotropin. It is believed to be a major fetal growth factor in contrast to Insulin-like growth factor 1, which is a major growth factor in adults".

Gene structure
In humans, the IGF2 is_associated_with::gene is located on is_associated_with::chromosome 11p15.5, a region which contains numerous imprinted genes. In mice this homologous region is found at is_associated_with::distal chromosome 7. In both organisms, Igf2 is imprinted, with expression resulting favourably from the paternally inherited is_associated_with::allele. However, in some human brain regions a loss of imprinting occurs resulting in both IGF2 and H19 being transcribed from both parental alleles.

The protein is_associated_with::CTCF is involved in repressing expression of the gene, by binding to the H19 imprinting control region (ICR) along with Differentially-methylated Region-1 (DMR1) and Matrix Attachment Region -3 (MAR3). These three is_associated_with::DNA sequences bind to is_associated_with::CTCF in a way that limits downstream enhancer access to the Igf2 region. The mechanism in which CTCF binds to these regions is currently unknown, but could include either a direct DNA-CTCF interaction or it could possibly be mediated by other proteins. In mammals (mice, humans, pigs), only the allele for insulin-like growth factor-2 (IGF2) inherited from one's father is active; that inherited from the mother is not — a phenomenon called imprinting.The mechanism: the mother's allele has an insulator between the IGF2 promoter and enhancer. So does the father's allele, but in his case, the insulator has been methylated. CTCF can no longer bind to the insulator, and so the enhancer is now free to turn on the father's IGF2 promoter.

Function
The major role of IGF-2 is as a growth promoting hormone during is_associated_with::gestation.

IGF-2 exerts its effects by binding to the IGF-1 receptor. IGF2 may also bind to the IGF-2 receptor (also called the cation-independent is_associated_with::mannose 6-phosphate receptor), which acts as a is_associated_with::signalling antagonist; that is, to prevent IGF2 responses.

In the process of folliculogenesis, IGF-2 is created by thecal cells to act in an autocrine manner on the theca cells themselves, and in a paracrine manner on granulosa cells in the ovary. IGF2 promotes granulosa cell proliferation during the follicular phase of the menstrual cycle, acting alongside follicle stimulating hormone (FSH). After ovulation has occurred, IGF-2 promotes is_associated_with::progesterone secretion during the luteal phase of the menstrual cycle, together with luteinizing hormone (LH). Thus, IGF2 acts as a co-hormone together with both FSH and LH.

A study at the Mount Sinai School of Medicine found that IGF-2 may be linked to memory and reproduction. A study at the European Neuroscience Institute-Goettingen (Germany) found that fear extinction-induced is_associated_with::IGF2/is_associated_with::IGFBP7 signalling promotes the survival of 17–19-day-old newborn hippocampal neurons. This suggests that therapeutic strategies that enhance IGF2 signalling and adult is_associated_with::neurogenesis might be suitable to treat diseases linked to excessive is_associated_with::fear memory such as is_associated_with::PTSD.

Clinical relevance
It is sometimes produced in excess in islet cell is_associated_with::tumors, causing is_associated_with::hypoglycemia. is_associated_with::Doege-Potter syndrome is a is_associated_with::paraneoplastic syndrome in which hypoglycemia is associated with the presence of one or more non-islet fibrous is_associated_with::tumors in the is_associated_with::pleural cavity. Loss of imprinting of IGF2 is a common feature in tumors seen in is_associated_with::Beckwith-Wiedemann syndrome. As IGF2 promotes development of fetal pancreatic beta cells, it is believed to be related to some forms of diabetes mellitus.

Interactions
Insulin-like growth factor 2 has been shown to interact with is_associated_with::IGFBP3   and is_associated_with::transferrin.