Female Reproductive Hormones

Female Reproductive Hormones

1. Function of the Ovaries

   • Production of female gametes (ova)
   • Production of female sex hormones - oestrogens and progesterone

2. The Ovarian Cycle

   • Primordial follicles made up of an oocyte surrounded by a single cell layer
     • 400 000 present in each ovary at menarche (first period)
     • After follicular selection the cells divide to form 2 layers - outer stromal cells and inner granulosa cell layer
       • A layer of theca cells (theca externa and theca interna) develops between the 2 layers and oocyte is surrounded by zona pellucida
         • Follicular antrum develops and fills with follicular fluid
           • Mature oocyte is suspended in the follicular fluid and attached to the granulosa layer by a stalk
             • During ovulation the follicle ruptures and releases the oocyte
               • The antrum fills with blood, forming a corpus haemmorrhagicum
                 • Develops into the corpus luteum
                   • Corpus luteum regression forms the corpus albicans
   • Oestrogens are the main secretory product of the developing follicle
     • Secreted by theca and granulosa cells
       • Theca cells release testosterone which is converted to oestradiol by granulosa cells
   • Progesterone is the main secretory product of the corpus luteum

3. Ovarian Steroidogenesis

   • Cholesterol
     • Pregnenolone
       • Progesterone
         • 17-alpha-hydroxyprogesterone
           • Androstenedione
       • 17-alpha-hydroxypregnenolone
         • DHEA
           • Androstenedione
             • Oestrone (via Aromatase)
               • In
             • Testosterone
               • 17-beta-oestradiol (via Aromatase)
                 • equilibrium

4. Control of Steroidogenesis

   • GnRH stimulates release of LH and FSH (low-pulse requency for FSH, high pulse-rate for LH)
     • LH increases testosterone production
       • Conversion to oestradiol in granulosa cells
         • Oestradiol inhibits gonadotrophs and GnRH
     • FSH increases oestradiol production in granulosa cells

5. Action of Oestrogens

   • Development and maintenance of secondary sex characteristics
   • Stimulation of breast development during puberty/pregnancy
   • Maintain structure and secretory function of vaginal mucosa
   • Promote uterine development (stimulate endometrial cell proliferation)
   • Increase libido
   • Important for bone health

6. Actions of Progesterone

   • Maintenance of pregnancy
   • Normally inhibits the proliferative effects of oestrogens
   • Facilitates ovulation

7. Ovarian Peptide Hormones

   • Inhibin
     • Secreted by granulosa and theca cells of developing follicle
     • Increases FSH release
   • Relaxin
     • Stimulates follicular development and oocyte maturation
       • May have a role in implantation
   • Activin
     • Produced by ovary and endometrium
       • May have a role in endometrial development

8. Menstrual Cycle

   • Generallly 28 days
   • 2 phases
     • Follicular phase
       • Variable length
     • Luteal phase
       • Always 14 days
   • Ovulation occurs halfway through the cycle - between the phases
   • LH and FSH remain at a low level and peak at ovulation. LH levels are higher than FSH levels
   • Oestradiol levels increase until a peak at ovulation, second smaller, less steep peak starts at ~day 17
   • Progesterone increases rapidly immediately after ovulation, plateaus between days 17-25 before a sharp decrease to a low level
   • The endometrium grows between days 5-14 and breaks down between days 1-5
   • Mean body temperature increases during ovulation

9. Ovulation

   • Occurs on day 14
   • Preceded by an increase in oestrogen
     • Triggers a GnRH/LH surge
       • LH surge stimulates ovulation
         • Increases synthesis of COX2 - involved in prostaglandin synthesis (especially PGEs)
           • Bind to EP2 receptor - increases cAMP
           • COX2/EP2 knockout mice can't ovulate
       • Acts on GnRH secreting neurones in the hypothalamus
         • Not a direct action of oestrogen - mediated by oestrogen-responsive neurones
           • Use kisspeptin as a transmitter
             • Kisspeptin stimulates GnRH release
   • Positive feedback