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Hormones of Testes - Testosterone Lecture NO: 2nd MBBS
Dr Muhammad Ramzan
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Testosterone – the definition
Testosterone is a steroid hormone , secreted primarily from the Leydigs’ cells of the Testes Belongs to the Androgen group and develops the male primary and secondary sex characters
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Testosterone – the background
Testosterone is the anabolic hormone and stimulates the growth of long bones, muscle mass and strength The male sex hormone is essential for puberty Testosterone is essential for the sex differentiation of the fetus during the 2nd trimester
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Testosterone - the properties
Gonadal steroids exist in free as well as in bound form Bound forms are associated with Steroid Hormone Binding Globulin- SHBG= 60% and Albumen 38% Free hormone diffuses into the cell - 2% Testosterone is altered to Dihydrotestosterone (DHT) in the target organs - is active metabolically
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Testosterone – the target tissues
Are those tissues with Testosterone/ androgen receptors Major tissues are : male gonads; bones, skeletal muscles, skin and adipose tissues GIT, brain and mammary gland
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Testosterone – The Biosynthesis
Cholesterol is the primary precursor of all the steroids in human body and is present in the testes and blood The site of Reactions is: the mitochondria and endoplasmic reticulum of the testicular Leydigs’ cells
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Testosterone – the Biosynthesis
Cholesterol is converted to Pregnenolone by the Cholesterol Desmolase Pregnenolone is altered to progesterone Progesterone is converted to 17- Alfa - Hydroxy progesterone and to Androstenedione Androstenedione is converted to Testosterone Testosterone to Dihydrotestosterone – DHT- the active form
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Testosterone - the biosynthesis
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Testosterone- conversion to DHT
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Testosterone – the regulation
Testosterone is regulated through 2 pathways Neuroendocrine/long loop/Indirect pathway Direct / short loop pathway (Through negative food back mechanism )
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Neuroendocrine /Long loop regulation
Is the interaction B/W circulating level of Testosterone and Hypothalamic – Pituitary – Leydigs' Axis Low Testosterone level stimulates the hypothalamic nuclei to release GnRH to activate Pituitary for : Gonadotropins FSH and LH LH and FSH activates Pituitary to ↑ Testosterone level Opposite is true when Testosterone level is high by the release of GnIH
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Testosterone - Neuroendocrine regulation
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Direct /short loop pathway Pituitary- Leydigs cells axis
It is the interaction B/W the circulating levels of Testosterone and LH and FSH from the anterior pituitary High testosterone level inhibits the LH from the pituitary and inhibits the synthesis of Testosterone from Leydigs cells Opposite is true when its circulating level is low Inhibin from the Sertoli cells inhibits the release of LH and Testosterone
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Short loop regulation of Testosterone
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Testosterone – mechanism of action in general
Testosterone is a sex steroid and its mechanism of action is similar to the rest of the steroids There is conversion of Testosterone to Dihydrotestosterone first in the target tissues It acts by activation of the genes, transcription of mRNA and its translation for specific proteins/enzymes to execute the specific action of Testosterone
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Testosterone – mechanism of action
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Testosterone – Mechanism of action
Free testosterone enters the Leydigs’ cells by diffusion and is converted to its active form – the DHT DHT binds with the Cytoplasmic receptors to form Hormone Receptor Complex – HRC HRC is translocated to the acceptor site at the DNA strand – Hormone Response Element (HRE)
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Testosterone - Mechanism of action- cont.
It activates the gene (HRE) to transcribe mRNA mRNA manages to get out of the nucleus and binds with the ribosome in the cytoplasm Translation of mRNA leads to the production of new proteins and enzymes to execute the actions of hormone
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Testosterone – the metabolic role
Testosterone is a anabolic hormone having effects on Protein synthesis and muscle growth Metabolism of Calcium (Long bones) Effect on water and electrolyte balance
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Testosterone - Protein synthesis muscle growth
Testosterone is an anabolic hormone and enhances the protein synthesis Promotes the growth / development of muscle mass and hypertrophy of muscles Testosterone ↑ the muscle mass by 50% in males as compared to females It ↑ the deposition of protein in the skin
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Testosterone – action on Ca++ metabolism Promotes Osteogenesis
Testosterone ↑ Ca++ reabsorption from the distal renal tubule ↑ Ca++ is deposited in the bone matrix, making the bones heavier and thicker in males It ↑ the length of the long bones especially in growth spurts like puberty Prevents osteoporosis
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Testosterone – effects on water/electrolyte balance
Testosterone ↑ the reabsorption of Sodium(Na) and water from distal renal tubules ↑ the blood volume in males by 5-10% as compared to females
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Testosterone - Secretion abnormalities
A very small amount of Testosterone is secreted before puberty both in boys and girls Puberty is associated with an ↑ secretion of Testosterone in boys Testosterone may be secreted in excess or there can be deficiency of secretion
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Testosterone – the excess the causes
Androgen excess is predominantly an endocrine disorder In women of reproductive age Androgens are more commonly produced from adrenal cortex and ovaries ( in such cases) Weak androgens are converted to potent androgens by the target tissues like adipose tissue, skin and muscles
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Testosterone – the excess
Androgen excess affects different target tissues /organs and produces reproductive dysfunction Others effects are : Acne and Hersutism Oily skin due to excessive secretion of Sebum Scalp hair line like male
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Excess of testosterone - Acne
Acne is a common skin disease, characterized by pimples on the face, chest, and back. It occurs when the pores of the skin become clogged with oil; Sebum, dead skin cells and bacteria.
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Testosterone excess in female - Acne
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Testosterone excess – ↑oily skin and Sebum
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Scalp hair line like males
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Testosterone excess- Hirsutism
It is the excessive growth of facial or body hair Is commonly due to overproduction of male sex hormones - the androgens (adrenal cortex and ovaries) Medication and disease Have irregular menstrual cycle
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Hirsutism
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Testosterone – the deficiency Hypogonadism
Deficiency of Testosterone is called as Hypogonadism It is characterized by the fall of testosterone below age specific- related level Results in failure to develop gonads and secondary sex characteristics Reduction in the muscle mass and strength ↑incidence of obesity and DM
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Hypogonadism - Retarded moustaches and beard
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