unit 1: hypothalamic anterior pituitary hormones Flashcards
what is the anterior pituitary, and its other name
adenohypophysis
- its the glandualr, anterior lobe
- both anterior and poterior are controlled by the hypothalamus
- anterior pituitary gland is a heterogenerous collection of numerous cell types that have the capacity to respond to specific stimuli and release hormones into systemic circulation
- there are various hypothalamic releasing or inhibiting factors which alter hormone secretion pattern of one or more anterior pituitary glands
what do neurosecretory cells secrete
- neurosecretory cells in the hypothalamus secrete releasing and inhibiting hormones to the anterior pituitary by way of capillary network and a portal vein
- these hormones then stimulate the anterior pituitary to secrete its own hormones whcih control other endocrine glands
describe the hypothalamic pituitary portal system
- neurons in hypothalamus release regulatory factors that are carried by yhe hypothalamic pituitary portal system to the anterior pituitary gland -> control the release of anterior pituitary hormoes
- posterior pituitary hormones are synthesized in cell bodies of the supraoptic and paraventricular neurons in the hypothalamus and then trandported down axonal pathways to terminals in the posterior pituitary gland
- hormones are stoed in post gland and from there released into systemic circulation
*there are separate vascular supplies to the anterior and posterior lobes
what does cortcio-releasing hormone release and what is the target organ
releaes adrenocorticotropin (ACTH) which targets the adrenal cortex
what does thyrotropin-releasing hormone release and what is the target organ
- thyroid stimulating hormone that tragets the thyroid gland
what does growth hormone releasing hormone (GHRH) release and what is the target organ
rleases growth hormone that targets the liver
what does somatotropin-releasing hormone release and what is the target organ
also GH and targets the GI system
what does gonadotropin releasing hormone release and wahts the target rogan
releases FSH and LH that targets the gonads
what does ghrelin release and what does it target
releases GH and targets the liver
what does dopamine releae adn whats the target organ
dopamine releases prolactin and targets the breast
describe the regulation of the anterior pituitaty organ axis
- regualted by the hypothalamus and the peripheral ttarget organs that the gland has an effect on through negative feedback loops
- therapeutic interventraion can occur at various sites within the axis, including activation or inhibition of releading or stim hormones
- stimuli @ hypo -> activation of AP -> sectretion of circulating hormone -> targets the target organ
what causes endocrine diseases
- result from the disruption of the reflex pathway such as hormone hypersecretion and hyposecretion or inappropriate target tissue response
what is usually the couse of hypersecretion? what is usually the cause of hyposecretion?
hypersecretion often result of primary (adrenal adenoma) or secondary (pituitary adenoma) tumors
- hyposecretion can result from primary glad malfunctions like autoimmune destruction (diabetes, thyroid), congenital disorders or surgery (thyroi, gonads), age dependent strophy (gonads) and toxicities or nutritional basis (thyroid)
*secondary and teritary gland malfunction is also possible
what can result from inappropriate target tissue response
can result from recepor expression abnormalities (such as ovarian tumors expressing GnRH receptors), mutated receptors or can be iatrogenic (resulting from activity of a physician) like a drug therapy of insulin and glucocorticoids
what can glucocorticoids be used to treat?
- inflammation, allergic reactions, septic shock, immunosupression (prevent organ transplant rejection)
- also used for non endocrine disease like cancer therapy bc of anti-lymphocytic effect in certain hemotologic malignancies like lymphona or multuple myelomas
endocrine drugs to treat cancer
- glucocorticoids can have anti-lymphocytic effects in certain hematologic malignancies such as lymphoma or multiple myelomas.
- antiestrogens and anti-androgens bind to increased estrogen and androgen receptors in the therapy of breast and prostate cancer respectively
describe the GH axid
hypothamic secretion of GHRH or ghrelin stimulates release of GH (also sex steroids during puberty and dopamine)
- release of somatostatin inhibits release of GH
- secreted GH stimulates the liver to synthesize and secrete insulin-like growth factor IGF-1, promoting systemic growth
- IGF-1 inhibits GH release from anterior pituitary gland
*hypoglycemia, sleep, exercise and adequate nutritional status also increase GH secretion
*hyperglycemia, sleep deprivation and poor nutritional status also inhibit GH release
pathophysiology of growth hormone deficiency
- failure to secret GH or enhance IGF-1 release during puberty results in growth retardation
- often due to defective hypothalamic release of GHRH (tertiary deficiency) or from pituitary insufficiency (secondary deficiency)
* failure of IGF-1 secretion in response to GH cannot be treated with GH
- pediatric indications for GH deficiency are: idiopathic short ntature, chronic kidney disease, turner syndrome and prader-willi syndrome
drugs to treat GH deficiency
- Sermorelin (synthetic GHRH) can be administered parenterally - got discontinued
- instead prescribing glucagon, arginine, clonidine and insulin induced hypoglycemia to stimulate GH release
Tesamorelin (novel GHRH analogue) used in treatment of HIV associated lipodystrophy
Somatropin is a recplacement recombinant human growth hormone, but short half life and very expensive
mecasermin is an effective treatment for patients with GH insensitivity (Lardon dwarf)
Pathophysiology of growth hormone excess
- often result of a somatotroph adenoma
- gigantism occurs if GH is secreted at abnormally high levels in children beore closure of epiphyses bc of inc IGF-1 levels promote excessive longitudinal bone growth
- after epiphases close abnoramlly high levels of GH result in acromegaly, IGF-1 cnt stim long bone growth but can promote organs and cartilaginous tissue
- inc hand thickness, englarging shoe size, hyperhidrosis, fatigue, macroglossia, organomegaly
treatment for growth hormone excess
- if somatotroph adenoma, can do a surgical resection, medical therapy, and radiation therapy
- transsphenoidal surgical resection of the adenoma is current treatment
- medication is Somatostatin receptor ligands (SRLs), inhibt GH secretion ex: octreotide and lanreotide
*somatostatin itself is rarely used bc half life is only a few min
pasireotide = somatostatin analogue first approved to treat Cushings disease but now effective for acromegaly
pegvisomat GH analoge that has bene modifed to bidn to one site on GH receptor w/ higher affinity tht native mol, but other bidnign site it inactive -> pegvisoman binds tightly to monomeric GH receptor but prevents dimerization required for activation (acts as competitive antagonist)
^Most potent IGF-1 reducing potntial, ut inc GH levels be dec IGF-1 mediated feedback
adverse effects of SRLs
GnRH axis
GnRH is secreted by the hypothalamus in a pulsatile fashion - stimulating gonadotroph cells of ant pit to secrete LH and FSH
- LH and FSH stimulate the ovaries and testes to produce sex hormones estrogen and testosterone, inhibiting further release of LH and FSH
- inc enstrogen levels secreted from deveoping follicles during follicular phase can cause positive feedback - midcycle ovulatory surge of LH anf FSH
- exogenous pulsatile GnRH can be used to induce ovulation in women with ifnertility of hypothalamic origin
- cont administration of GnRH suppresses the gonadoroph response to endogenous GnRH causing dec production fos ex hormones
