Sex Steroids: Testosterone, oestrogen and progesterone Flashcards
Key Roles of Sex Steroids
Promote sexual differentiation
Development of secondary sexual characteristics
Regulate sexual behaviour
Supporting normal reproductive function
Support bone growth and maintain bone mass
Core Structure of sex steroids
Cyclopentanoperhydrophenanthrene ring also called the steroid nucleus or sterane.
Aromatase is the enzyme that converts testosterone to oestrogens (aromatisation)
Oestradiol is the main oestrogen that is active in the body and is the one that is measured in blood tests.
Actions of Steroid Hormones
Most of the steroids have receptors within the nucleus, and the action that occurs because of this interaction is called a genomic action. Steroid hormone being lipophilic passes through the plasma membrane and the nuclear membrane and interacts with the receptor in the nucleus. The receptors are polypeptides that have a domain that binds to the steroid hormones. So after binding to the domains of the receptors they bind to DNA sequences, creating a hormone response element. This hormone response element induces transcription creating mRNA that will be translated into an effector protein that bring about physiological effects.
What do the proteins created from sex steroids act on?
Proteins acts on:
Skin
Bone
Teeth
Cardiovascular
Metabolic
Immune system (anti-inflammatory effects)
Communication between genomic and non-genomic actions
Genomic actions can take a few hours to happen where as non-genomic actions occur very quickly. An example would be oestrogen which can have directly affect the G protein coupled transmembrane receptors. As a result of stimulation of this G protein receptor, there is a signal transduction and there is a cascade of different kinases producing physiological effects within the cell. Interestingly, you can also see that the nuclear receptors within the cytosol can interact with the hormone and can directly effect growth factors on the plasma membrane and results in calcium fluxes across plasma membranes leading to physiological effects.
Testosterone
It is produced by Leydig cells in testicles and theca interna cells of ovaries
Testosterone secretion is under control of LH (luteinizing hormone) a pituitary glycoprotein hormone
Testosterone secretion has pulsatile, diurnal and circadian rhythms, highest concentrations on waking up and lowest in the afternoon, evenings.
Functions of Testosterone
During embryonic development, it regulates the differentiation of the Wolffian ducts into epididymis, vas deferens
It promotes somatic growth and virilisation in boys
It is essential for maintaining sexual function & germ cell development.
It regulates secondary sexual/non-sexual characteristics and muscle growth.
Hypothalamic-Pituitary-Testicular Axis
The hypothalamus, contains the GnRH pulse generator. GnRH stands for Gonadotropin releasing hormone is secreted in a pulsatile manner. This has a direct effect on the anterior pituitary , leading on to the secretion of the gonadotropins, which are LH (luteinizing hormone) and FSH (follicle stimulating hormone). The luteinizing hormone stimulates the Leydig cells to produce androgens which can be aromatised by aromatase to produce testosterone.
What is the important role of androgens in the hypothalamic-pituitary testicular axis?
Androgens play an important role in Sertoli cells (also called nurse cells) that nurse the growth of the spermatogonia into sperm and provides the nutrition for the sperm. Sertoli cells have the enzyme aromatase in them which produces small concentrations of oestrogens within the cell. Sertoli cells produce androgen binding cells which tend to maintain a reasonably good concentration of testosterone within the testicles. This is important for the development of sperms and spermatogenesis.
How is the hypothalamic-pituitary-testicular axis regulated?
Sertoli cells also produce inhibin which have a negative feedback on FSH and androgens have negative feedback on secretion of LH and GnRH.
Oestrogens
Oestrogens - Oestrone, Oestradiol, and Oestriol, main type is oestradiol.
Predominant production in ovaries by granulosa cell, also produced locally in tissues.
Oestradiol also produced from conversion of circulating androgens by aromatization
Secretion is under the influence of LH and FSH, which are gonadotropins hormones secreted by the anterior pituitary.
Functions of Oestrogens
It regulates secondary sexual female characteristics & sexual behaviour
It is responsible for secretory activity within the genital tract
It regulates GnRH secretion, and is responsible for ovulation during the menstrual cycle
Regulates cardiovascular physiology and neuronal growth, bone structure and integrity.
Hypothalamic-Pituitary-Ovarian Axis
The area of the brain that is responsible for the GnRH pulse generator is the hypothalamus. The hypothalamus stimulates anterior pituitary gland to secrete follicle stimulating hormone (FSH) and luteinizing hormone (LH). The luteinizing hormone in women stimulates the Theca cells within the ovarian follicle. The ovarian follicle has the oocyte, Granulosa cells and over the granulosa cells you have the theca cells. The luteinizing hormone stimulates the Theca cells to stimulate the release of androgens and progestins. Androgens and FSH stimulate Granulosa cells to make oestrogens. Granulosa cells also contribute to the pool of progestins in the body.
Progestins
Progestins are a collective term used for the different types of progesterone such as progesterone-like hormones but progesterone being the main hormone within the family of progestins.
How is the hypothamaic-pituitary-ovarian axis regulated?
Granulosa cells in women secrete inhibin which has negative effects on FSH whereas secretion of activins have a positive feedback on anterior pituitary. Oestrogens play an important role in feedback as they can have positive or negative effect on anterior pituitary and hypothalamus.
