Download presentation
Presentation is loading. Please wait.
1
Steroid Hormones
2
Objectives Recall the overall role of steroids in human body.
Understand the physiological roles of cholesterol especially in synthesis of steroid hormones. Recall the biochemical and clinical aspects of all types of adrenal steroids. Explain with appropriate details the biochemical and physiological aspects of steroids from the testis and ovaries Recognize the biochemical and clinical relations of congenital adrenal hyperplasia and testicular feminization syndrome
3
Steroid Hormones Types of steroid hormones:
Glucocorticoids: cortisol is the major representative in most mammals Mineralocorticoids: aldosterone being most prominent Sex hormones: Androgens: such as testosterone Estrogens: including estradiol & estrone Progestogens: also known a progestins such as progesterone
4
Steroid Hormones Steroid hormones are synthesized in:
All steroid hormones are: Derived from cholesterol & differ only in the ring structure & side chains attached to it. Lipid soluble & thus are freely permeable to membranes so are not stored in cells Steroid hormones are synthesized in: Adrenal cortex: cortisol, aldosterone & androgens (androstendione) Testis: testosterone Ovaries: estrogens & progesterone Placenta: progesterone Some peripheral tissues (as adipose tissue & the brain)
5
Steroid Hormones Cholesterol is the precursor of steroid hormones
6
Transport of Steroid Hormones in Blood
Steroid hormones have to be carried in the blood complexed to specific binding plasma proteins (globulins). Cortisol: by corticosteroid binding globulin (transcortin) Sex steroids (testosterone & estradiol): by sex hormone-binding protein (SHBG) Aldosterone: by the plasma protein albumin
7
General Functions of Steroid Hormones
Steroid hormones play important roles in: Metabolic regulation (glucocorticoids i.e. cortisol) Electrolyte balance (mineralocorticoids i.e. aldosterone) Reproductive functions (gonadal steroids i.e. testosterone & estrogens) Steroids also play roles in: Inflammatory responses Stress responses Bone metabolism Cardiovascular fitness Behavior, cognition & mood
8
Steroid Hormone Synthesis
A series of enzymatic steps in the mitochondria & ER of steroidogenic tissues convert cholesterol into all of the other steroid hormones & intermediates. An important control point this process is the transport of free cholesterol from the cytoplasm into mitochondria. This step is carried out by the Steroidogenic Acute Regulatory Protein (STAR)
9
Sources of Cholesterol for Steroid Synthesis
Lipoproteins in Blood Sources of Cholesterol for Steroid Synthesis LH Acetyl CoA Cholesterol pool ATP cholesterol cAMP Protein Kinase mitochondria STAR Desmolase Pregnenolone Pregnenolone In: Adrenal Cortex Testis Ovary ALL STEROID HORMONES
10
Steroid Hormone Synthesis
The first enzymatic step is the conversion of cholesterol to pregnenolone which occurs in the mitochondria. This reaction is carried out by the enzyme desmolase This is a rate limiting, nonreversible step in the initiation of steroid biosynthesis. This step occurs in Adrenal Cortex, Ovary & Testis
11
Steroid hormone synthesis in the Adrenal Cortex
12
The adrenal gland is composed of the adrenal cortex & adrenal medulla
Organization of the Adrenal Gland The adrenal gland is composed of the adrenal cortex & adrenal medulla 1- The adrenal cortex: The zona glomerulosa: secretes aldosterone The zona fasciculata: secretes cortisol The zona reticularis: secretes the adrenal androgens 2- The adrenal medulla: Secretes adrenaline (epinephrine) As you knowthe adrenal gland is:
13
Cholesterol Steroid Hormone Synthesis In Adrenal Cortex Pregnenolone
Desmolase Pregnenolone 3-β-Hydroxysteroid dehydrogenase Progesterone 21-α-Hydroxylase 17-α-Hydroxylase 17-α-Hydroxyprogesterone 11-Deoxycorticosterone androgen 21-α-Hydroxylase Androstenedione 11- β -Hydroxylase 11-Deoxycortisol Testosterone Corticosterone NOT IN ADRENAL CORTEX Peripheral Tissues Aldosterone Cortisol Estradiol
14
Regulation of Cortisol Secretion from the Adrenal Cortex
Negative feedback control: ACTH release from the anterior pituitary is stimulated by hypothalamic secretion of corticotrophin releasing hormone (CRH). CRH ACTH Cortisol Cortisol (or synthetic steroids) Suppress CRH & ACTH secretion Hypothalamus Pituitary Adrenal
15
Testosterone Production in the Testis
16
Pathway of Testosterone Production in the Testis
The production of androgens from cholesterol is identical to that in the adrenal, except that it continues from androstenedione to testosterone. Cholesterol In the Testis Androstenedione Testosterone 17b-hydroxysteroid Oxidoreductase N.B. In the adrenal cortex, androstendione (adrenal androgen) is formed. They are released to blood & converted in the testis (& peripheral tissues) to testosterone
17
Pathway of Testosterone Production in the Testis
The main steroid produced in the male is testosterone produced from the testis. . In the male, there is peripheral conversion of testosterone to: Dihydrotestosterone: in androgen target tissues, like muscles by 5 a reductase Or to Estradiol : mostly in adipose tissue by enzyme cytochrome P450 aromatase
18
Control of Testicular Function by the Pituitary Gonadotrophins (LH & FSH)
Hypothalamus GnRH LH ++ testosterone synthesis in testis FSH ++ spermatogenesis in testis + - Anterior Pituitary FSH LH + + Testis Testosterone ++ Spermatogenesis ++ Development of secondary male sex characters ++ Anabolism Testosterone Spermatogenesis +
19
Synthesis of Steroid Hormones in the Ovary
20
Synthesis of Steroid Hormones in the Ovary
Estradiol is formed from the conversion of androgens (testosterone) into estradiol by the enzyme cytochrome P450 aromatase (in granulosa cells). The androgens required for conversion come from the neighboring theca cells. Cholesterol Theca Cells Androstendione Testosterone Estradiol Aromatase Stimulated by FSH Stimulated by LH Granulosa Cells of the Ovary
21
Synthesis of steroid Hormones in the Ovary
LH ++ estrogen secretion ++ ovulation FSH ++ secretion of estrogen Regulates growth of ovarian follicle Theca cells Granulosa LH LH receptor cholesterol Androstendione Androstendione Testosterone FSH aromatase Estradiol FSH receptors LH & FSH stimulates estrogen secretion FSH regulates growth of ovarian follicles LH stimulates ovulation
22
Mechanism of Action of Steroid Hormones
Cytosolic Receptors Hormone Receptor Complex HRE of genes Transcription of genes is increased
23
Congenital Adrenal Hyperplasia (CAH)
It is the result of an inherited enzyme defect in steroid hormones biosynthesis in the adrenal cortex. The Adrenal Cortex : Cannot secrete cortisol absent negative feedback to the pituitary) ACTH continues to drive steroid biosynthesis adrenal hyperplasia & accumulation of cortisol precursors (depending on which enzyme is lacking) Cannot secrete aldosterone electrolyte disturbances The condition might be fatal unless diagnosed early
24
21 -Hydroxylase Deficiency
17-hydroxy-progesterone Progesterone Androstenedione In Peripheral Tissues 21 -hydroxylase 11-deoxycorticosterone 11-deoxycortisol Testosterone Aldosterone Cortisol Precocious sexual development in ♂ Virilisation of ♀
25
21 -Hydroxylase Deficiency
Accounts for ~ 95% of all cases of CAH Autosomal recessive condition Low or absent synthesis of Cortisol & Aldosterone Cortisol ACTH secretion Adrenal Gland hyperplasia Some of the accumulated precursors are diverted to the biosynthesis of sex hormones Signs of Androgen Excess: stimulation of adrenal androgen production virilisation in baby girls & precocious puberty in boys In severe cases, Aldosterone Deficiency is evident salt & water loss hypovolaemia & shock neonatal adrenal crisis
Similar presentations
© 2024 SlidePlayer.com Inc.
All rights reserved.