LECTURE 8 (Female hormones) Flashcards
Describe the embryological development of ovarian eggs
1) During foetal life, outer surface of ovary is covered by a GERMINAL EPITHELIUM (embryologically derived from epithelium of germinal ridge) + PRIMORDIAL OVA differentiate from germinal epithelium and migrate into OVARIAN CORTEX
2) Each ovum collects round it a layer of spindle cells from the OVARIAN STROMA + takes on epitheliod characteristics
[called Granulosa cells at this point]
3) Ovum surrounded by a single layer of granulosa cells is called a “Primordial follicle” or “Primary oocyte” -> after follicular growth it becomes “Primary follicles”
4) During reproductive years of life (13-46 years), follicles develop to expel their ova + remainder become degenerate/”atretic”
[in menopause, only a few primordial follicles remain in ovaries + degenerate soon after]
What are the three different types of hormones?
- Gonadotropin-releasing hormone (GnRH)
[hypothalmic releasing hormone] - Follicle-stimulating hormone (FSH) + Luteinising hormone (LH)
[anterior pituitary sex hormones + secreted in response to GnRH] - Oestrogen + Progesterone
[secreted by ovaries in response to LH and FSH]
Describe the release of GnRH
- Released from hypothalamus increased and decreases much less drastically during the monthly sexual cycle
- Secreted in short pulses every 90 minutes
What is “Menarche”?
The time of the first menstrual cycle
What happens when LH and FSH bind to their receptors in ovarian target cell membranes?
- Increase the cells’ rates of secretion
- Growth + proliferation of cells
- Activation of cyclic adenosine monophosphate second messenger system in cytoplasm -> formation of protein kinase + multiple phosphorylations of key enzymes that stimulate sex hormone synthesis
Describe the ovarian egg cells during childhood
Granulosa cells provide nourishment for the ovum + secrete an oocyte maturation-inhibiting factor to keep the ovum in its primordial state in the PROPHASE stage of meiosis
What is the effect of increased secretion of LH and FSH?
- Accelerated growth of 6-12 primary follicles each month
- Rapid proliferation of granulosa cells -> gives rise to more layers
- Spindle cells derived from ovary interstitium collect in several layers outside granulosa cells -> forms “theca” (2 layers)
[Theca Interna = epithelioid characteristics + develop ability to secrete oestrogen and progesterone, Theca Externa = develops into highly vascular connective tissue capsule that becomes the capsule of the developing follicle]
ADDITIONAL INFO: The early growth of the primary follicle up to the ANTRAL STAGE is stimulated mainly by FSH alone
What happens after the proliferative phase of growth?
- Mass of granulosa cells secretes a FOLLICULAR FLUID that contains a high concentration of oestrogen
- Accumulation of fluid causes an ANTRUM to appear within the mass of granulosa cells
- Greatly accelerated growth occurs, leading to larger follicles called VESICULAR FOLLICLES
What is accelerated growth of follicles into “vesicular follicles” caused by?
- Oestrogen secreted into the follicle causes granulosa cells to form increasing numbers of FSH receptors -> makes granulosa cells more sensitive to FSH
- Pituitary FSH and oestrogens combine to promote LH receptors on original granulosa cells -> allows LH stimulation to occur alongside FSH stimulation -> rapid increase in follicular secretion
- Increasing oestrogens from follicle + increasing LH from anterior pituitary -> proliferation of follicular thecal cells
What happens in Atresia?
1) Large amounts of oestrogen from the rapidly growing follicle act on the HYPOTHALAMUS to depress further enhancement of FSH secretion -> blocks further growth of less well developed follicles
2) Largest follicle continues to grow because of INTRINSIC POSITIVE FEEDBACK EFFECTS + all other follicles stop growing and involute
EXPLANATION: Atresia is important because it prevents multiple pregnancies
What happens shortly before ovulation?
Protruding outer wall of follicle swells rapidly + “stigma” (small area in center of follicular capsule) protrudes like a nipple -> Fluid oozes from follicle through the stigma -> Stigma ruptures widely, allowing a vicious fluid to evaginate outwards -> Vicious fluid carries with it the ovum surrounded by a mass of several thousand small granulosa cells called “Corona radiata”
What happens during ovulation?
-
What happens 2 days before ovulation?
- The rate of secretion of LH by the anterior pituitary gland increases markedly
- FSH increases 2-3 fold
- FSH and LH act synergistically to cause rapid swelling of the follicle during the last few days before ovulation
What happens before ovulation occurs?
- Rapid growth of follicle
- Diminished oestrogen secretion after prolonged phase of excessive oestrogen secretion
- Initiation of secretion of progesterone
Which two events occur that are necessary for ovulation?
- Theca externa begins to release proteolytic enzymes from lysosomes -> cause dissolution of follicular capsular wall + consequent weakening of wall -> further swelling of entire follicle + degeneration of stigma
- Rapid growth of new blood vessels into follicle wall + prostaglandins secreted into follicular tissues -> plasma transduction into follicle + follicle swelling
FOLLICLE SWELLING + DEGENERATION OF STIGMA -> FOLLICLE RUPTURE -> DISCHARGE OF OVUM
What happens during the “Luteal phase” of the cell cycle?
- After release of ovum, granulosa and theca interna cells change into “Lutein cells” [LUTEINISATION] where they grow + fill with lipid giving a yellow colour [becomes “CORPUS LUTEUM”]
(dependent on LH + inhibited by luteinisation-inhibiting factor) - Granulosa cells -> develop extensive intracellular smooth endoplasmic reticula that form large amounts of progesterone and oestrogen
- Theca cells -> form androstenedione and testosterone (androgens)
[most are converted by AROMATASE in oestrogen]
What happens to the Corpus Luteum?
- Grows to 1.5cm 7-8 days after ovulation
- After 12 days of ovulation, begins to involute + loses secretory function + yellow lipid characteristic
[becomes “corpus albicans”] - Replaced by connective tissue and over months is absorbed
What inhibits the anterior pituitary gland from secreting FSH and LH?
- Oestrogen and progesterone (lesser extent)
- Inhibin
EXPLANATION: Low blood concentrations of both LH and FSH cause the corpus lute to degenerate completely [“involution” of corpus luteum]
What is the difference in functions between oestrogens and progestins?
- Oestrogens = promote proliferation + growth of specific cells in the body responsible for the development of most secondary sexual characteristics of female
- Progestins = prepare uterus for pregnancy + breasts for lactation
Describe the synthesis of Oestrogen and Progesterone
- Steroids synthesised from cholesterol + small portion from Acetyl-CoA
- Mainly progesterone and testosterone and androstenedione are synthesised first -> during follicular phase, most converted to oestrogen by AROMATASE in granulosa cells -> Lack of aromatase in theca cells, androgens diffuse into adjacent granulosa cells for conversion
- During luteal phase, too much progesterone is formed for all to be converted -> high conc in blood
How are Oestrogen and Progesterone transported in blood?
Bound to plasma albumin and with specific progesterone and oestrogen-binding globulins
ADDITIONAL INFO:
binding between hormones is loose enough to rapidly release to tissues over a period of 30 minutes
What are the functions of the liver in oestrogen degradation?
- Conjugates oestrogens to form glucuronides and sulphates -> excreted in bile + urine
- Converts potent oestrogens, Estradiol and Estrone, into almost totally potent estriol
ADDITIONAL INFO:
Decreased liver function increases the activity of oestrogens in the body (HYPERESTRINISM)
