Browsing Pathways

Glucocorticoids are a class of steroid hormones that includes cortisol. These hormones bind to specific receptors in cells, called glucocorticoid receptors, which are present in various tissues throughout the body. When cortisol or other glucocorticoids bind to these receptors, they can exert their effects on metabolism, immune function, inflammation, and other physiological processes. The glucocorticoid pathway is essential for regulating these functions and maintaining homeostasis in the body. Cortisol, a steroid hormone, is synthesized from cholesterol. It is synthesized in the zona fasciculata layer of the adrenal cortex. Adrenocorticotropic hormone (ACTH), released from the anterior pituitary, functions to increase LDL receptors and increase the activity of cholesterol desmolase, which converts cholesterol to pregnenolone and is the rate-limiting step of cortisol synthesis. The majority of glucocorticoids circulate in an inactive form, bound to either corticosteroid-binding globulin (CBG) or albumin.[2] The inactive form is converted to its active form by 11-beta-hydroxysteroid dehydrogenase 1 (11-beta-HSD1) in most tissues, while 11-beta-HSD2 inactivates cortisol back to cortisone in the kidney and pancreas. When cortisol binds to the glucocorticoid receptors in the body, it elicits a wide range of physiological and metabolic effects. These effects are part of the body's response to stress and play essential roles in maintaining homeostasis. Major effects that occur naturally are metabolism regulation, wherein Cortisol promotes the breakdown of fats and proteins to provide energy for the body. It also stimulates gluconeogenesis, which is the production of glucose from non-carbohydrate sources, such as amino acids and glycerol. This helps maintain blood glucose levels; anti-inflammatory response wherein cortisol suppresses the immune system's inflammatory response by inhibiting the production of pro-inflammatory cytokines and other mediators of inflammation, immunosuppression wherein cortisol inhibits the activity of immune cells, such as lymphocytes and leukocytes, which can help reduce immune responses. This effect is beneficial in controlling autoimmune reactions but can also make the body more susceptible to infections. Others are stress response and blood pressure regulation, anti-allergic response, tissue repair and modulation of mood and cognitive functions.

Histamine is a biogenic amine synthesized from L-histidine exclusively by L-histidine decarboxylase, which uses pyridoxal-5’-phosphate as a cofactor. Histidine decarboxylase is widely expressed throughout various cells in the body, such as gastric mucosa, neurons, parietal cells, mast cells, and basophils. Modulation of histamine’s effect occurs through four types of receptors: H1, H2, H3, and H4. Histamine receptors are G-protein coupled receptors, which are 7-transmembrane chain proteins that mediate the effect of several molecules. H1 receptors are Gq coupled receptors. Its downstream effects are mediated by increased activity of phospholipase C, increased cytoplasmic calcium, and a subsequent increase in protein kinase C activity.[8] H2 receptors are Gs-coupled receptors. Its downstream effects are mediated by an increase in intracellular cAMP and activation of protein kinase A.[5] Both H3 and H4 receptors are G protein-coupled receptors. A decrease in intracytoplasmic cAMP mediates the downstream effects of histamine. H2RAs decrease gastric acid secretion by reversibly binding to histamine H2 receptors located on gastric parietal cells, thereby inhibiting the binding and activity of the endogenous ligand histamine. H2 blockers thus function as competitive antagonists. Normally, after a meal, gastrin stimulates histamine release from enterochromaffin-like cells, which then binds to histamine H2 receptors on gastric parietal cells and leads to gastric acid release. This increase in gastric acid release occurs through the activation of adenylate cyclase, which raises intracellular cAMP levels. cAMP then activates protein kinase A (PKA), which, among other functions, phosphorylates proteins involved in the movement of H+/K+ ATPase transporters to the plasma membrane. The increase of H+/K+ ATPase transporters at the plasma membrane allows for the secretion of more acid from parietal cells. By blocking the histamine receptor and thus histamine stimulation of parietal cell acid secretion, H2RAs suppress both stimulated and basal gastric acid secretion induced by histamine. Antagonists of histamine H2 receptor antagonist are used to treat gastroesophageal reflux disease and various ulcers. They display more selectivity towards H2 histamine receptors compared to other H1 anti-histamines. After being taken orally, They are absorbed in the GI tract and travel through the blood to get to the stomach epithelium. They block the downstream Gs cascade which produces cyclic adenosine monophosphate (cAMP) which is an activator for the potassium-hydrogen ATPase pump (H+/K+ ATPase pump). The pump is responsible for secreting hydrogen ions into the stomach lumen increasing the acidity of the stomach environment. By blocking adenylate cyclase signalling pathway from the histamine H2 receptor less hydrogen ions are secreted into the stomach lumen increasing the pH. The less acidic environment doesn't irritate the stomach as much. The H+/K+ ATPase pump can still be activated through gastrin and acetylcholine through the phospholipase C signalling pathway, but blocking the adenylate cyclase pathway helps reduce the acidity.

Trying to draw Vitamin D pathway in skin

The hypothalamic–pituitary-gonadal axis (HPG axis) is an integrated pathway that examines the brains regulation over the reproductive system in males and females. Kisspeptin neurons in the hypothalamus activate gonadotropin-releasing hormone (GnRH) neurons to secrete GnRH. GnRH acts in the anterior pituitary to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These two hormones act on different gonadal cells. In the testes, FSH acts on Sertoli cells to stimulate spermatogenesis and LH acts on Leydig cells to secrete testosterone. In the ovaries, LH acts on Theca cells to secrete androgens and FSH acts on Granulosa cells to convert those androgens to estrogen. FSH also influences oocyte development.

Test

Progesterone is an endogenous steroid hormone that is commonly produced by the adrenal cortex as well as the gonads, which consist of the ovaries and the testes. Progesterone is also secreted by the ovarian corpus luteum during the first ten weeks of pregnancy, followed by the placenta in the later phase of pregnancy. The conversion of progesterone generation from the corpus luteum to the placenta generally occurs after week ten. The molecule progesterone is a derivative of cholesterol and has numerous functions in the human body, especially within the reproductive system. Molecules of progesterone form from the process of steroidogenesis. Progesterone plays a vital role in the maintenance of the uterus during pregnancy. A progestogen (also called progestagen, gestagen, or gestogen) is a molecule, either natural or synthetic, that shows similar effects as progesterone, binds to the progesterone receptor and acts as an agonist. Progestins are synthetic progestogens. Progesterone utilizes intracellular receptors for their mode of action. Progesterone crosses the membrane of a target cell readily by passive diffusion through the plasma membrane due to its lipophilicity and then binds to and activate progesterone receptors. When unbound, the progesterone receptor exists as a monomer. After binding progesterone, the receptor undergoes a conformational change and becomes a dimer, which increases receptor binding to DNA. Most progestins exert their contraceptive effects by suppressing the secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the pituitary gland. This suppression alters the menstrual cycle to suppress ovulation. This progesterone and receptor complex then transports to the nucleus and binds to DNA, specifically near the promoter regions of genes that contain enhancers, containing hormone response elements. This binding of the complex to the promoter can either enhance or repress transcription, which ultimately alters the production of proteins.