End

Front 1

The Hypothalamic-Pituitary-Thyroid (HPT) Axis

3 parts

Back 1

Hypothalamus- Thyrotrope- Thyroid

Front 2

Hypothalamic releasing factor

Back 2

Thyrotropin-Releasing Hormone (TRH)

Acts on Thyrotrope

Front 3

Anterior pituitary trophic hormone

(2) and function

Back 3

Thyrotropin

Thyroid-Stimulating Hormone(TSH)

Stimulates thyroid follicle cell growth and thyroid hormone synthesis. TSHover-stimulation leads to thyroid hyperplasia (goiter).

Front 4

Thyroid gland hormone (2)

Back 4

thyroxine (T4)

tri-iodothyronine (T3)

main bioactive thyroid hormone; primarily formed bydeiodination of T4 in peripheral tissues

Front 5

Thyroid hormone actions

Back 5

a.) Brain development

b.) Increase metabolic rate

c.) Increase muscle contractility and excitabilityd.) Necessary for normal growth: stimulate growth hormone secretion and cartilage &bone deposition

Front 6

Hypothalamic-Pituitary-Thyroid axis regulation

Feedback inhibition

Back 6

Primarily by triiodothyronine (T3), which isgenerated by deiodination in TRH neurons and thyrotropes.

Front 7

Iodine deficiency and regulation

Back 7

ultimately reduces thyroid hormone levels

stimulates the activity of endocrine of the thyroid axis byrelieving feedback inhibition of TSH (& TRH). IncreasedTSH stimulate the thyroid gland to increase in size (forming a goiter) and activityto make as much thyroid hormones as it can.

Front 8

The Hypothalamic-Pituitary-Gonadal (HPG) Axis

Hypothalamic releasing factor:

Back 8

Gonadotropin-releasing hormone (GnRH)

Front 9

Kallmann's syndrome

Back 9

a genetic form of infertility, is associated with anosmia (nosense of smell) and is caused by failure of the GnRH neurons to migrate from theolfactory placode into the hypothalamus.

Front 10

The Hypothalamic-Pituitary-Gonadal (HPG) Axis

Anterior pituitary trophic hormones

Back 10

Gonadotropins

FSH & LH

Front 11

Follicle-Stimulating Hormone (FSH)

Back 11

regulates gametogenesis (production &development of germ cells) and induces LH receptors on steroidogenic cells

1.) Men: spermatogenesis

2.) Women: ovarian follicle development

Front 12

Luteinizing Hormone (LH)

Back 12

regulates steroidogenesis

1.) Men: testosterone synthesis by Leydig cells

2.) Women: estrogen and progesterone synthesis by the ovary

Front 13

Target gland hormone: gonadal steroids

Back 13

a.) Men: testosterone

b.) Women: estrogen, progesterone

Front 14

Gonadal Steroid Actions

Back 14

a.) Fetal differential of male external genitalia

b.) Development of secondary sex characteristics, i.e. those important for sexualbehavior or nourishing infant, but NOT required for fertility

c.) Maturation of gametes & reproductive organs

d.) Pubertal growth spurt and epiphyseal plate closure

Front 15

Pituitary-Gonadal (HPG) Axis

Negative feedback

Back 15

gonadal steroid feedback inhibit LH, GnRH

Inhibin inhibit FSH

Front 16

Inhibin

Back 16

produced by ovarian granulosa cells andthe testicular Sertoli cells, the target cells for FSH

Front 17

Gonadal inhibition by Prolactin

Physiologica vs Pathological

Back 17

a.) Physiological --lactation-associated amenorrhea (lack of menstrual cycles)

b.) Pathological—prolactinoma (prolactin-secreting tumor). The most commonpituitary tumor

Front 18

Hypothalamic-Pituitary-Adrenocortical (HPA) axis

Hypothalamic releasing factors

Back 18

Corticotropin-releasing hormone (CRH): mostpotent

Vasopressin--9 amino acid hypothalamicpeptide. Weak ACTH-releasing activity on itsown but synergizes with CRH

Oxytocin--9 amino acid hypothalamic peptiderelated to vasopressin; synergizes with CRH

Front 19

Hypothalamic-Pituitary-Adrenocortical (HPA) axis

Anterior pituitary trophic hormone

Back 19

Adrenocorticotropin (ACTH)

stimulates growth and glucocorticoidsecretion of cells in the zona fasciculata of theadrenal cortex

Front 20

Hypothalamic-Pituitary-Adrenocortical (HPA) axis

Target gland hormone

Back 20

Cortisol

Other layers of the adrenalcortex make mineralocorticoid and androgen steroids, but these are not normallyregulated by ACTH.

Front 21

Glucocorticoid actions (general)

Back 21

Glucocorticoids are “stress hormones”

Glucocorticoids are also involved in infant development & nutrition:

Front 22

Hypothalamic-Pituitary-Adrenocortical Axis Regulation

Stimulation v. Inhibition

Back 22

Stimulated by stress

Feedback inhibition: Cortisol inhibits ACTH, CRH, and vasopressin

Front 23

The Growth Hormone (GH) Axis

Hypothalamic regulatory factors

Stimulation v. Inhibitory

Back 23

a.) Stimulatory: Growth-hormone-releasing hormone (GHRH)

b.) Inhibitory: Somatostatin

Front 24

The Growth Hormone (GH) Axis

Anterior Pituitary Hormone

Back 24

Growth Hormone (GH)

Front 25

The Growth Hormone (GH) Axis

Target gland hormone

Back 25

Insulin-like Growth Factor-I (IGF-I, a.k.a somatomedin C)

Front 26

GH target tissues

Back 26

the liver is a major source or IGF-I, butmany other tissues also produce IGF-I & probably contribute to growth effects

Front 27

IGF-I actions

Back 27

IGF-I stimulates protein synthesis and tissue growth by endocrine, paracrine, &autocrine actions

Before adulthood: linear growth of bones

After fusion of epiphyseal plates: soft tissue growth only.

Front 28

GH actions

Back 28

GH promotes the availability of substrates & energy for growth- has little growth promotingactivity by itself except via stimulating IGF-1

Front 29

GH Axis Regulation

Negative feedback

Back 29

inhibition of GHRH and stimulation of somatostatin

IGF-I acts directly at somatotroph and indirectly at hypothalamus (↓ GHRH; ↑somatostatin) to decrease GH secretion

Front 30

4 Other GH regulators

Back 30

1.) Thyroid hormone--required for normal GH expression and synthesis;hypothyroidism reduced GH secretion

2.) Sleep- GH increases during slow-wave (stage N3) sleep

3.) Glucose – GH is inhibited by elevated glucose, stimulated by hypoglycemia

4.) Arginine-arginine stimulation is used as clinical test for GH deficiency

Front 31

Prolactin hypothalamic inhibitory factor

Back 31

PRL secretion is controlled only via inhibition by dopamine from tuberoinfundibular dopamine (TIDA) neurons

Front 32

Prolactin actions

Back 32

PRL stimulates proliferation and differentiation of mammary alveolar epitheliumduring pregnancy

Front 33

Galactorrhea

Back 33

milk-like secretion a pathophysiological effect of prolactin excess.Growth hormone is structurally related to PRL and at high levels, can alsocause galactorrhea. However, PRL has no growth-promoting activity.

Front 34

Vasopressin actions

Back 34

a.) Water reabsorption (V2 vasopressin receptors): stimulates externalization ofaquaporin-2 water channels on the apical membrane of collecting duct cells

b.) Arteriolar constriction (V1 vasopressin receptors)c.) ACTH secretion

c.) ACTH secretion

Front 35

Desmopressin

Back 35

synthetic V2 receptoragonist

Front 36

Central DI diabetes insipidus

Back 36

caused by damage to vasopressin neurons(tumors, surgery; pituitary stalkcompression) or by genetic deficiency.

Front 37

Nephrogenic DI

Back 37

occurs when thekidney cannot respond normally tovasopressin (e.g., impaired expression/function of V2 receptors or aquaporin2)

Front 38

Oxytocinactions

Back 38

a.) Uterine contraction during parturition

b.) Milk ejection ("let-down") reflex

d.) ACTH secretion

Front 39

Oxytocin regulation: sensory neural circuits

Back 39

i.) Oxytocin secretion during delivery stimulated by cervical dilation

ii.) In lactating females, oxytocin is stimulated by baby’s crying or suckling

iii.) During stress, oxytocin is stimulated by stress-activated afferents to thehypothalamus

Front 40

3 Layers of Adrenal Cortex

Back 40

zona glomerulosa

zona fasciculata (middle)

zona reticularis (inner most)

Front 41

zona glomerulosa Secretion

Back 41

aldosterone

zona glomerulosa is regulated by the Renin-Angiotensin-Aldosterone axis RAAaxis

Front 42

zona fasciculata Secretion

Back 42

cortisol,

zona faciculata is regulated by the Hypothalamic-Pituitary-Adrenocortical (HPA)axis

Front 43

zona reticularis Secretion

Back 43

1) weak androgens

2) dehydroepiandrosterone(DHEA)

3) androstenedione

Front 44

stimulateion of glucocorticoid secretion

Back 44

(ACTH) by activatingglucocorticoid synthesis and by stimulating adrenocortical growth

Front 45

How does ACTH stimulates glucocorticoid synthesis

Back 45

a.) Stimulates cholesterol uptake

b.) Stimulates expression & activity of proteins responsible for conversion ofcholesterol to pregnenolone

Steroids not stored, made de novo

Front 46

How does ACTH stimulate adrenocorotical growth

Back 46

increases size (hypertrophy) and number(hyperplasia) of zona fasciculata cells Significant adrenal atrophy occurs within days of the loss of ACTH

Front 47

3 hypothalamic releasing factors that control ACTH

Back 47

CRH- most potent

Vasopressin- synergizes with CRH

Oxytocin- structurally similar to ADH

Front 48

Glucocorticoid secretion is inhibition

Back 48

glucocorticoid negative feedback

Decreases the following:

1) ACTH secretion/ expression

2) Synthesis and secretion of CRH

3) Synthesis and secretion of Vasopressin

Front 49

glucocorticoid bound by

Back 49

Only free, unbound glucocorticoids are bioactive

globulin- CBG.transcortin - produced by liver

Albumin- main plasma transport for Aldosterone

Front 50

Glucocorticoids action mechanism

Back 50

Glucocorticoid andmineralocorticoid receptorsfunction as ligand-dependenttranscription factors.

In theunbound form, they reside in thecytoplasm

Once bound byhormone, they translocate to thenucleus and interact with othertranscription factors to increaseor decrease gene expression & protein synthesis

Front 51

Glucocorticoid actions

Back 51

Increase blood glucose, fatty acids, amino acid

Front 52

Primary Hypothyroidism

Back 52

Thyroid hormone deficiency due to deficits in thyroid gland.

Most common cause US: Autoimmune

Most common cause worldwide: Iodine deficiency

Front 53

Secondary Hypothyroidism

Back 53

Thyroid hormone deficiency due to deficits in thyrotrope or TRH neurons (hypothalamus)

Front 54

Primary Hyperthyroidism

Back 54

increased thyroid hormone due to thyroid tumor

Front 55

Secondary Hyperthyroidism

Back 55

TSH-secreting pituitary tumor

TSH will be elevated, or excessive for give level of thyroid hormones

Front 56

Graves Disease

Back 56

Most common cause of hyperthyroidsm

Antibodies that stimulate TSH receptor cause increased thyroid hormone secretion

TSH suppressed due to elevated thyroid hormone

Front 57

Thyroid-Binding-Globulin where is it synthesized

which has higher affinity for TBG? T3 or T4

Back 57

Synthesized and secreted by the Liver

T4 has higher affinity, also increase T4 halflife

Front 58

2 additional Thyroid hormone binding protein

Back 58

Transthyretin

Albumin

Front 59

2 major Thyroid hormone receptors

Back 59

THR alpha

mediate thyroid hormone action outside hypothalamus and pituitary

THR beta

Mediates negative feedback of thyroid hormone at TRH neurons and Thyrotropes

Front 60

Dual control of Adrenal Medulla

Back 60

Neural: Adrenal chromaffin cell innervated by sympathetic pre-ganglionic cholinergic neuron in splanchnic n.

Endocrine: Glucocorticoids stimulates epinephrine synthesis.

Front 61

Rate limiting step and Enzyme in Catecholamine synthesis, location of synthesis

Back 61

Adrenal Medulla

Tyrosine-Hydroxylase catalyzes rate limiting step.

Tyrosin to DOPA

Front 62

Enzyme that convert Noepi to Epi

Back 62

PNMT

expression is induced by glucocorticoids

Front 63

Norepinephrine re-uptake in neural tissues

Back 63

NET

re-uptake by noradrenergic neurons

90% of norepinephrine re-uptake

Front 64

Catecholeamine uptake in peripheral tissue

Back 64

EMT

OCT

Glucocorticoids inhibit activity

prolonging catecholamine action

Front 65

Metabolism Neuron vs peripheral

Back 65

Neurons only express MAO

Peripheral express MAO & COMT

Front 66

Norepinephrine metabolite from MAO

Back 66

DHPG

Front 67

Epinephrine & Norepinephrine metabolite from COMT and liver

Back 67

Epi = MN

Norepi = NMN

Both metabolized by liver to VMA