unit 1: hypothalamic anterior pituitary hormones

Question 1

what is the anterior pituitary, and its other name

Answer 1

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

Question 3

what do neurosecretory cells secrete

Answer 3

• 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

Question 4

describe the hypothalamic pituitary portal system

Answer 4

• 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

Question 5

what does cortcio-releasing hormone release and what is the target organ

Answer 5

releaes adrenocorticotropin (ACTH) which targets the adrenal cortex

Question 6

what does thyrotropin-releasing hormone release and what is the target organ

Answer 6

• thyroid stimulating hormone that tragets the thyroid gland

Question 7

what does growth hormone releasing hormone (GHRH) release and what is the target organ

Answer 7

rleases growth hormone that targets the liver

Question 8

what does somatotropin-releasing hormone release and what is the target organ

Answer 8

also GH and targets the GI system

Question 9

what does gonadotropin releasing hormone release and wahts the target rogan

Answer 9

releases FSH and LH that targets the gonads

Question 10

what does ghrelin release and what does it target

Answer 10

releases GH and targets the liver

Question 11

what does dopamine releae adn whats the target organ

Answer 11

dopamine releases prolactin and targets the breast

Question 12

describe the regulation of the anterior pituitaty organ axis

Answer 12

• 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

Question 13

what causes endocrine diseases

Answer 13

• result from the disruption of the reflex pathway such as hormone hypersecretion and hyposecretion or inappropriate target tissue response

Question 14

what is usually the couse of hypersecretion? what is usually the cause of hyposecretion?

Answer 14

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

Question 15

what can result from inappropriate target tissue response

Answer 15

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

Question 16

what can glucocorticoids be used to treat?

Answer 16

• 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

Question 17

endocrine drugs to treat cancer

Answer 17

• 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

Question 18

describe the GH axid

Answer 18

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

Question 19

pathophysiology of growth hormone deficiency

Answer 19

• 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

Question 20

drugs to treat GH deficiency

Answer 20

• 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)

Question 21

Pathophysiology of growth hormone excess

Answer 21

• 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

Question 22

treatment for growth hormone excess

Answer 22

• 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

Question 23

adverse effects of SRLs

Question 24

GnRH axis

Answer 24

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