The Hypothalamic Pituitary Axis Higher brain centers aka the central nervous system stimulate the hypothalamus where set points are stored The Hypothalamus secretes tropic hormones to communicate with pituitary which then secretes hormones to individual endocrine glands Tropic hormones cause release of another hormone Humoral control also affects hormone release Something in the blood that is not a tropic hormone causes hormone secretion parathyroid hormone calcitonin release by low high calcium insulin glucagon release by high low blood sugar Hormone release may also be regulated by circadian rhythms light dark cycles Established by the pineal gland located just next to the optic chasm A stress is considered as any change from homeostasis Hypothalamic Hormone Thyrotropin releasing hormone TRH Corticotropin releasing hormone CRH Gonadotropin releasing hormone GnRH Growth Hormone releasing hormone GHRH Growth Hormone Inhibiting Hormone GHIH somatostatin Prolactin stimulating hormone PRF PRH Prolactin inhibiting hormone PIH dopamine GPCR Gq Anterior Pituitary Releases thyrotropin TSH and prolactin Gs Gq Gs Gi Releases corticotropin ACTH Releases LH and FSH gonadotropins Releases growth hormone Inhibits release of growth hormone not well known Gi Releases prolactin Inhibits release of prolactin The pituitary gland hangs from the hypothalamus and has two functional lobes The posterior pituitary is nervous tissue and secretes oxyctocin and AHD The anterior pituitary is glandular tissue and secretes TSH ACTH FSH LH GH Prolactin and Endorphins Hypothalamus synthesizes neurohormones released in pulsatile fashion contains groups of functionally distinct cells called nuclei Oxytocin and ADH are synthesized as preprohormones then transported to posterior pituitary and stored GnRH deficiency GnRH can be suppressed by stress drugs alcohol Early in life leads to delayed onset of puberty Later in life leads to infertility more pronounced in women amenorrhea anovulation which can lead to ovarian failure due to insufficient estrogen The posterior pituitary releases oxytocin and antidiuretic hormone ADH Both are nonapeptides 9 amino acids with similar structures that differ only by two amino acids Oxytocin Synthesized as preprooxyphysin Stimulates o Uterine contractions in labor o Milk ejection into breast ducts o Smooth muscle contraction of vas deferens May also act to facilitate sperm transport in uterus in non pregnancy state Also associated with love pairbonding trust and maternal behavior Hyposecretion o leads to low milk production and difficult labor o linked to autism as lack of social interaction Nasal spray of oxyctocin has been shown to improve social behavior of children with autism Hypo and hypersecretion associated with autoimmune diseases Vassopressin ADH Osmolarity is more important to maintain than blood pressure because electrolyte concentration affects nervous system function Promotes water reabsorption by kidneys acts on V2 receptors by Gs Causes vasoconstriction acts on V1a recptors by Gq using calcium as second messenger Decreases osmolarity increases BP Secretion is stimulated by o Increase in osmolarity from normal 285 mosm kg o Large decrease in blood volume o Decrease in blood pressure Vasopressin has also been linked to love and monogamy Moles that have fewer V1a receptors leads to vasoconstriction were more promiscuous This is because they live on the mountain where water is plentiful and can mate whenever they want have plenty of babies that will survive Moles who live on the prairie have more V1a receptor because they do not always get a lot of water have to be more conservative and protect their babies Hypersecretion leads to serum hypervolemia hypo osmolarity and with vasoconstriction hypertension Hyposecretion leads to central diabetes insipidus polyuria inability to concentrate urine bedwetting normally more ADH is released at night so you don t pee yourself Molecular Effects of ADH on the Kidney High osmolarity low blood pressure ADH secretion Gs increases cAMP Activates protein kinase Aquaporin 2 is produced and inserted into the apical membrane Water can cross apical membrane from kidney collecting duct into principle cells lining the duct Water crosses baslateral membrane exits cell on other side by aquaporin 3 Water is reabsorbed by plasma in peritubular capillary Decreases osmolarity increases BP The anterior pituitary releases six hormones Two affect non endocrine targets growth hormone and prolactin The other four are tropic hormones thyroid stimulating hormone adrenocorticotropic hormone Leutinizing hormone follicle stimulating hormone Growth Hormone Pulsatile release greatest during sleep Increases blood glucose o Inhibits glycogen synthesis o Inhibits insulin receptor production o Inhibits glucose uptake by muscle o Stimulates liver gluconeogenesis o Hypersecretion may cause DM Indirect Effects o Increases cell division and tissue growth Stimulates synthesis of IGF I insulin like growth factor I which increases clonal expansion of chondrocytes in growing end plates of long bones o Increases amino acid uptake protein synthesis o Increases fatty acid release from adipose tissue and utilization by muscles o Increases fibroblast differentiation to chondrocytes to form cartilage then form bone Secretion increases by o Hypoglycemia o Puberty o Estrogen testosterone Secretion decreases by o Hyperglycemia o Circulating fatty acids sensitivity to insulin Hyposecretion Hypersecretion o In childhood gigantism o In adulthood acromegaly Laron syndrome is an insensitivity to growth hormone due to a mutation of the receptor Children with hypoglycemia can be treated with GH because GH deficiency causes increased o In childhood dwarfism o In adulthood decreased muscle mass low bone density Growth Hormone Receptor Pathway Growth hormone binds receptor Receptor dimerizes Self phosphorylation of janus tyrosine kinase JAK Phosphorylation and dimerization of STAT kinases Dimer translocation into the nucleus Activation of transcription factors Increased gene expression Growth proliferation and differentiation self phosphorylation of JAK also leads to SHC kinase activation MAPK cascade IRS PI3 kinase pathways All of which cause metabolic changes that eventually contribute to growth proliferation and differentiation SHP tyrosine phosphorylase inactivates the growth hormone receptor by removing PO4 both the receptor and JAK This causes an end to the signal Prolactin 3 from