L8 Endocrine Physiology of the Ovary Flashcards
Granulosa Cell (Ovary) Hormone Production?
FSH Responsive => Increased Estradiol
Granulosa Cells are Analogous to Sertoli cells in Males
Estrogen
- Essential for normal reproductive function: Follicular Growth, Endometrial growth
- Development of Reproductive Tissue
- Secondary Sexual Characteristics
- Mammary Gland Development
Inhibin: Negative feedback regulation of FSH
Luteal Cells (Ovary) Hormone Production?
Progesterone
- Essential for normal reproductive function: Endometrial Development
- Maintains pregnancy (till placental competency)
- Mammary Gland Development
Ovarian Follicles Stages?
Primordial Follicles
- Have entered first stage of meiosis , further progress arrested
- Hormones cause meiosis I to resume in several follicles =>Meiosis II by ovulation
- Penetration by sperm causes the final stage of meiosis to occur
Growing Follicles
Early Primary Follicle
- Primary oocyte surrounded by unilinear granulosa
- Follicle separated by basal lamina
Late Primary Follicle
- Granulosa cells separated by distinct basement membrane
- Surrounding stroma cells differentiate into Theca Interna and Theca Externa
Secondary (Antral) Follicle
- Fluid-filled Antrum develops (DEFINING FEATURE OF SECONDARY FOLLICLES)
Mature (Graafian/Tertiary) Follicles
- Influenced by FSH and LH some secondary follicles develop into Graafian Follicles
- Completes First phase of Meiosis (previously arrested)
- Oocytes is now secondary oocyte => secondary meiotic division begins
- Oocyte, Zona Pellucida and Attached granulosa cells are expelled at ovulation
Importance of Theca Interna?
Theca Externa: Darker Staining- Fibrous
Theca Interna: Larger and paler staining - Endocrine
Theca Interna is an important endocrine cell secreting androgens that are converted to estrogen by granulosa cells (requires BOTH pituitary gonadotropins FSH and LH)
- LH => Androgen synthesis in Thecal Cells
- FSH => Conversion of Androgens to estrogen in Granulosa Cells
Thecal Cells (Ovary) Hormone Production?
LH responsive=> Increased Androgens
Analogous to Leydig Cells
Female Endocrine Cell analogous to the Leydig Cell?
Thecal Cells (responsive to LH) => Androgen Production
Female Endocrine Cell analogous to the Sertoli Cell?
Granulosa Cells (Responsive to FSH) => Estradiol/Inhibin Production
KEY ENZYMES of Ovarian Steroid Hormone Synthesis
Estradiol: produced in the Ovarian Follicle (by Granulosa Cells)
- 17b hydroxysteroid dehydrogenase required to convert Estrone => Estradiol
Progesterone: produced in the Corpus Leuteum
- 3b hydroxysteroid dehydrogenase required
Aromatase (Granulosa Cells) converts androgens to Estradiol
Endocrine Cells of the Ovary?
Hormones they Respond to?
Hormones they synthesize?
Thecal cells:
- Respond to LH (Anterior Pituitary)
- Synthesizes Androgens => output to granulosa cells for conversion to estrogen
- DO NOT produce aromatase: cannot convert androgens to estrogen
Granulosa cells:
- Respond to FSH (Anterior Pituitary)
- Limited capacity to synthesize Estrogen from cholesterol
- HIGH levels of aromatase: able to convert androgens (thecal cells) to Estrogen
Endocrine Cells of The Corpus Luteum (Luteal Cells)?
Corpus Luteum: Transient endocrine gland of the postovulatory ovary
Cell types:
Thecal Lutein Cells: Cholesterol => Androstenedione (converted to estradiol in Granulosa)
Granulosa Lutein Cells: Produces mainly PROGESTERONE, also ESTRADIOL
Life Cycle of Corpus Luteum (Fertilization vs. No Fertilization)
Under influence of pituitary gonadotrophins (FSH, LH) => Corpus Luteum begins to secrete progesterone (lesser amounts of estrogen)
NO Fertilization
Sufficient levels of Estrogen and Progesterone reached => LH secretion inhibited by negative feedback regulation
=>Lack of LH triggers demise of CL=> degenerates into non-functional Corpus Albicans
Fertilization/Implantation of Ovum rescues Corpus Luteum
After implantation embryo secretes LH like hormone (Chorionic gonadotropin hCG) => acts upon CL => continued progesterone production
CL remains a significant source of progesterone till the developing placenta takes over in the late 1st semester
_________ is major ovarian steroid before menopause
Effects?
Estradiol is major ovarian steroid before menopause
- decelerates linear growth
- closes epiphyseal growth plate
- increases bone density
- promotes adipose tissue deposition
- stimulates growth of reproductive tissues
- stimulates breast development
Control of Ovarian Endocrine Function?
GnRH released by Neuroendocrine cells in arcuate nucleus of hypothalamus => Stimulates LH and FSH Section (Gonadotroph cells of Anterior Pituitary)
- LH => Thecal Cells
- FSH => Granulosa Cells
Regulation of the Early Follicular Phase of Ovarian Cycle?
- Feedback inhibition of LH by estrogen is WEAK => stimulation remains constant/increases during follicular phase despite rising estrogen levels
- Feedback inhibition of GnRH secretion from hypothalamus by estrogen => SMALL effect on LH secretion from the pituitary
- Feedback Inhibition of FSH secretion by estrogen is STRONG
Negative Feedback Requires both Estrogen AND Progesterone
Regulation of the Late Follicular Phase/Ovulation of Ovarian Cycle?
Presence of Progesterone means Corpus Leuteum or Placenta is secreting it indicating pregnancy (Mechanism of Birth Control )!!
Absence of Progesterone + high levels of estrogen stimulate pituitary LH (not FSH) production in POSITIVE FEEDBACK => LH surge=> OVULATION
Estrogen also acts on the hypothalamus to stimulate GnRH secretion => accentuates pituitary LH secretion and causes a modest rise in FSH
Regulation of Luteal Phase of Ovarian Cycle?
Only when both estrogen and progesterone levels are high (during luteal phase of cycle) is feedback inhibition of LH effective
Corpus luteum absolutely dependent on LH for continued survival
- Falling LH => demise of Corpus Luteum
- Implantation=> actions of hCG (Chorionic gonadotropin) from fetus after implantation can sustain Corpus Luteum
Oral Contraception Options?
Progesterone only pill
- low dose/short acting
- long acting/slow release
- main effects on cervix and gonadotrophin production
Combined OCP
- synthetic estrogen and progesterone (both required for maximum efficacy)
- primary action is to inhibit LH and FSH (no ovulation)
- secondary action on endometrium and cervix
Emergency Contraception (morning after pill)
- high dose Progesterone and/or Estrogen
mechanisms of action:
- delay/prevent ovulation
- alter endometrium to impair implantation
- RU486 (Mifepristone)
- Progesterone agonist that blocks action of Progesterone only pill
GnRH Deficiency (aka._______________) Pathogenesis/Symptoms
GnRH Deficiency: Kallman Syndrome
Inherited disorder of deficient GnRH production (GnRH triggers FHS/LH release from anterior pituitary gland)
Mutations in KAL1 gene interpheres with migration of GnRH secreting neurons to hypothalamus in development
Deficient GnRH production=> Lack of FSH/LH Production
Symptoms:
- Hypogonadotropic Hypogonadism (HH)
- Infertility
- Absent/Incomplete Pubertal Maturation
- 50% cases have Anosmia (Lack of Smell) - distinguishes from other HH
Hypopituitarism (aka. ______________) Pathogenesis/Symptoms/Treatment
Hypopituitarism: Sheehan’s Syndrome
Pathogenesis:
Postpartum hemorrhage => infarction and necrosis of pituitary gland => Less FSH and LH
Symptoms:
Present immediately or asymptomatic until additional insult/trauma:
- cessation of lactation
- amenorrhea/oligomenorrhea
- fatigue
- adrenal insufficiency
Treatment: Hormone replacement therapy
- T4
- cortisone
- gonadotrophins or estrogen + progesterone if resumption of normal ovarian cycling desired
Secondary Hypercortisolism (aka. ________________) Pathogenesis/Symptoms?
Secondary Hypercortisolism: Cushing’s Disease
Pathogenesis:
Secondary hypercortisolism due to ACTH excess=> ACTH stimulates cortisol AND androgen production=> increased negative feedback regulation by adrenal androgens in hypothalamus and pituitary => reduces LH and FSH production
Symptoms:
- Fertility Impaired: Amenorrhea
- Hirsutism (Facial Hair Growth)
Hyperprolactinemia Pathogenesis/Symptoms?
Pathogenesis
- 40% due to benign pituitary adenomas
- Other due to tumor/pathologies that lower dopamine levels
More stimulation of luteal cells than granulosa:
- Stimulates lactation
- Interferes w/ gonadal function (hypogonadism) by suppressing LH and FSH
Symptoms:
Females: Galactorrhea, Amenorrhea
Males: Decreased libido, Infertility
Congenital Adrenal Hyperplasia (CAH) Pathogenesis/Symptoms?
21a hydroxylase deficiency=> Excessive buildup of Androgens =>
- sexual ambiguity in females
- adrenal androgens limit FSH and LH=> prevents/delays puberty and ovulation
Sexual Development and Fertility in CAH: due to increased adrenal androgens
Males
- precocious puberty in men (accelerated sexual development)
- high incidence of infertility
Women - Masculinization (virilization)
- ambiguous genitalia
- excessive facial hair, virilization
- menstrual irregularity in adolescence
- anovulation in adulthood
Most common form of chronic anovulation (ovaries don’t release oocyte) in women of reproductive age?
Polycystic Ovary Syndrome (PCOS)
Polycystic Ovary Syndrome (PCOS) Associations and Hormonal Implications?
Most common form of chronic anovulation in women of reproductive age
Associated with Obesity and Type II diabtes
Hyperandrogenism => Insulin resistance (COMMON)
Altered GnRH Pulse Rate
- LH INCREASED
- FSH - DECREASED (More stimulation of luteal than granulosa)
- Estrogen INCREASED
- Androgens INCREASED
- Insulin INCREASED
Pathogenesis of Menopause?
Natural process caused by aging and depletion of finite amount of oocytes
Ovarian follicles become unresponsive to pituitary gonadotrophins
- Lack of negative feedback by estrogen and inhibin leads to increased FSH and LH
- Aromatase (in adipose tissues) continues to convert androgens to estradiol, still a big drop off from prior levels
