8.4 Sex Steroid Hormones and Contraception Flashcards
(28 cards)
What are the 3 classes of sex steroid hormone
-androgens (e.g testosterone or dihydrotestosterone)
-oestrogens (e.g oestradiol or oestrone)
-progesterone
What are some non steroid reproductive hormones
GnRH, FSH, LH, inhibin, activin and AMH
What are the location of the primary synthesis of sex steroids
The primary synthesis of sex steroids occurs mostly in the gonads but is also produced in the adrenal glands.
Describe the primary synthesis of sex steroids in the adrenal gland
In the zona reticularis of the adrenal cortex, there are enzymes that are essential for producing DHEA which is a precursor for peripheral conversion to other androgens. The testes and ovaries have the enzyme 17β-HSD, which converts DHEA and androstenedione into testosterone and oestradiol. Adrenal production of sex steroids becomes particularly important in postmenopausal individuals when ovarian production declines. Adrenal sex steroid synthesis is regulated by adrenocorticotropic hormone (ACTH) from the pituitary gland.
Describe how the synthesis of sex steroids is regulated
Sex steroid synthesis is controlled by the pulsatile release of GnRH from the hypothalamus. The GnRH triggers the secretion of LH and FSH. FSH stimulates gamete production (via follicular development in the ovaries and acting on the sertoli cells to stimulate spermatogenesis in the testes). LH triggers ovulation & formation of corpus luteum in the ovaries and stimulates leydig cells to produce testosterone in the testes. These sex hormones themselves exert mostly negative feedback on the hypothalamus pituitary axis, although regulation is dynamic and can sometimes be positive in the menstrual cycle, ovulation & formation of corpus luteum in ovaries. Inhibin exerts negative feedback on the pituitary gland, specifically inhibiting FSH secretion. It is important for ensuring only a single dominant follicle matures in each menstrual cycle / helps regulate spermatogenesis
Describe testosterone
LH stimulates testosterone production from leydig cells. The subsequent enzymatic steps are similar to the adrenal androgen synthesis where ultimately 17β-HSD converts androstenedione to testosterone. In the testes, testosterone diffuses from Leydig cells to Sertoli cells to support spermatogenesis.
FSH stimulates Sertoli cells to produce Androgen-binding protein (ABP). This binds to testosterone, so maintaining high levels of testosterone within the seminiferous tubules, supporting spermatogenesis. 98% of circulating testosterone is bound to plasma proteins but only the free testosterone is biologically active.
What is the mechanism behind the genomic effects of sex steroid hormones.
They bind to receptors (androgen, oestrogen and progesterone respectfively) which are a family of transcription factors found in the cytoplasm of cells. The receptor then translocates into the nucleus upon activation.
Describe some of the genomic effects of testosterone
In the embryo - Causes the development of the male genital tract from the mesonephric duct
In the testis - Causes proliferation and differentiation of spermatogonia
In the bone - Directly affects osteoblasts and increases bone formation
In the muscle - Increases muscle mass and strength
In the bone marrow - Increases erythropoiesis
What are the 2 hormones that testosterone can be converted into
dihydrotestosterone (DHT) and oestradiol
What is dihydrotestosterone (DHT)
DHT is produced from testosterone via the 5a-reductase enzyme. DHT binds to the androgen receptor with a greater affinity than testosterone, making it more potent. It has prolonged effects due to its slower metabolism compared to testosterone.
Describe some of the genomic effects dihydrotestosterone
In the embryo - Causes development of external male genitalia during embryogenesis
In the prostate - Causes growth and maintenance which can be implicated in cancer and BPH (benign prostate hyperplasia)
In the hair follicles - Promotes facial hair and body growth + scalp hair loss
In the liver - It causes the metabolic regulation of androgens
What is oestradiol
Oestradiol is produced from testosterone via the aromatase enzyme in the testes, adipose tissue, bone, skin, muscle and brain. Estradiol binds to oestrogen receptors (ERα and ERβ), which belong to the same receptor superfamily as androgen receptors. There are differences in estradiol concentration, receptor distribution and sensitivity between males and females which influences physiological outcomes. In males it is essential for bone maintenance, libido and sperm development, in females it predominantly regulates reproductive and secondary sexual characteristics.
Describe some of the genomic effects of oestradiol
In the bone - promotes bone growth and maintenance
In the brain - it promotes libido
In adipose tissue - It influences fat distribution
In the testes - It supports spermatogenesis and inhibits apoptosis of developing sperm cells
Describe the non genomic effects of testosterone
These are rapid effects mediated through membrane-associated receptors or intracellular signalling pathways, occurring within seconds to minutes. They involve secondary messenger systems and are difficult to study due to their speed and complexity. The non genomic signalling can trigger pathways that ultimately influence gene expression. These include;
In blood vessels - causing vasodilation
In muscles - impacting muscle contraction via intracellular calcium levels
In immune cells - modulating immune cell function and inflammatory responses
What is one symptom of low testosterone in men
Low testosterone in men can cause osteoporosis. Treatments include testosterone therapy, lifestyle factor changes and calcium and vitamin D supplementation
Describe the 3 main oestrogen hormones
They are oestrone, β-oestradiol (aka oestrogen), and oestriol.
β-oestradiol is the most potent, common, and the primary circulating oestrogen in non-pregnant women. Small amounts are produced by the adrenals and adipose tissue. Oestrogens are metabolised in the liver where β-oestradiol and oestrone are converted into oestriol as it is less potent.
Oestriol is the most prominent during pregnancy and is produced by the placenta
Oestrone is the most prominent after menopause and is produced by adrenals and adipose tissue.
What are the genomic effects of oestrogens
In the female secondary sexual characteristics - causes growth in uterus, vagina and breasts, a change in the vaginal epithelium from cuboidal to stratified, increase in cilliated cells in the fallopian tubes, proliferation of endometrial glands
In body fat - it changes the distribution in females towards buttocks, hips and thighs
In bone - it causes epiphyseal closure, inhibits bone resorption and is critical for peak bone mass
In the skin - it increases vascularity, maintains skin thickness and elasticity
In the cardiovascular system - it regulates vascular tone and endothelial function, modulates lipid metabolism and cholesterol levels
In the brain - It regulates cognitive functions, mood, neuroprotection and modulates sexual behaviour
What is progesterone
Progesterone is the primary circulating progestogen, it is synthesised in the corpus luteum and placenta, it is a precursor for other steroid hormones including testosterone.
Describe the genomic action of progesterone
In the uterus - it promotes secretory changes in the endometrium to prepare the uterus for implantation and prevents premature uterine contraction
In the breast - it causes the proliferation of alveolar cells, secretory development and increases tissue fluid to prepare for lactation
In the ovaries - it supresses further ovulation during pregnancy
In the bone - it contributes to maintaining bone mineral density
In the cardiovascular system - it regulates vascular tone and lipid metabolism
In the central nervous system - it regulates mood and sleep
What are some of the non genomic effects of oestrogens
In immune system - they have anti-inflammatory effects
In the metabolism - they cause rapid glucose uptake in skeletal muscle
In the cardiovascular system - causes rapid vasodilation through activation of eNOS
What are some of the non genomic effects of progesterone
In the reproductive tract - increases sperm motility as they migrate through female reproductive tract
In the immune system - inhibits inflammatory cytokiine release to promote a tolerant environment during pregnancy
In the cardiovascular system - modulates vascular tone
What is the menstrual cycle
It is a monthly cycle resulting in the production of an ovum and thickening of the endometrium to allow for implantation should fertilisation occur. Each cycle lasts about 28 days, the cycle begins on first day of menstruation and ovulation occurs at about day 14. The cycle is regulated by the hypothalamic-pituitary-ovarian axis.
Describe the follicular phase.
It varies in length, between 10-21 days and causes the pulsatile release of GnRH from the hypothalamus which stimulates the anterior pituitary gland to release FSH and LH. FSH initiates recruitment & maturation of follicles and stimulates granulosa cells. LH stimulates theca cells to produce androgens and progesterone.
Describe how the follicular phase contributes to oestrogen synthesis
LH then stimulates theca cells to synthesise progesterone and androgens. The theca cells lack aromatose so the androgens diffuse into the granulosa cells which do have aromatase (the aromatase trancription is stimulated by FSH). The aromatase synthesises the oestrogens from androgens. Rising oestrogen levels negatively feedback to the anterior pituitary, inhibiting LH & FSH production.
