Folliculogenesis and Reproductive Hormones

Folliculogenesis

• Folliculogenesis, within the context of female endocrinology, exists to produce gametes for sexual reproduction.

The Ovary

• Oogenesis involves both the formation and development of female gametes (oocytes).

Learning Outcomes

• Ability to name and classify the main reproductive hormones.
• Understanding of the mode of action of reproductive hormones.
• Understanding of basic reproductive endocrinology.
• Brief understanding of the process of puberty.
• Brief understanding of Maternal Recognition of Pregnancy (MRP) process.

Reproductive Physiology

• Understanding the organs involved in the reproductive system including the brain, hypothalamus, pituitary, ovary (follicle, corpus luteum), and uterus.
• Understanding the importance of various hormones involved, such as leptin, melatonin, kisspeptin, opioids, GnRH, FSH, LH, oestrogen, progesterone and PG.

Hormones

• Categories include decapeptide (GnRH), glycoprotein (FSH/LH), and steroid (P4, E2, Test).

Reproductive (Oestrous) Cycle

• Highlights how the brain is influenced by factors such as light, stress, nutrition, dopamine and sex steroids.
• How the hypothalamus releases GnRH when Kisspeptin and Neurokinin Dynorphin are present.
• GnRH influences the pituitary gland triggering FSH and LH release.

Hormone Mode of Action

• Secrete H -> Blood -> Target Receptor -> Action

G-Coupled Protein Receptors

• Many peptide and protein-based hormones function via G-coupled protein receptors (GCPR's) on or within cell walls.

The Steroid Nucleus

• Steroid hormones have a base structure with three cyclohexane rings (A, B, C) and one cyclopentane ring (D).
• Steroid hormones act via soluble nuclear receptors and are fat soluble.

Reproductive Hormones

• Originate from the hypothalamus, pituitary, gonads, uterus, placenta, and adrenals/tumours.
• Classified by source, mode of action (e.g., gonadotrophin), and biochemical nature (e.g., glycoprotein).
• Act in minute quantities.
• Bind to specific receptors.
• Have short half-lives.
• Can influence each other directly or indirectly.

Changes in the Female Reproductive Tract

• The reproductive tract changes throughout life in response to hormones and pregnancy.
• Long-term changes include puberty, old age, and physical changes associated with gestation.
• Short-term changes include each oestrous cycle and changes during pregnancy and parturition.
• Oestrogen results in hydration of collagen and interstitial oedema.

Theory of Anatomical Variation with GnRH Release

• How GnRH is released specifically in females
• Understanding the Surge and Tonic centres

GnRH and LH Pulsatility

• Pulses of luteinizing hormone (LH) are always preceded by GnRH pulses.

Kisspeptin/GnRH Interaction

• The interaction between Kisspeptin fibres and GnRH neurons is a key part of the reproductive cycle

Recruitment

• Entry into a Gonadotropin Sensitive Pool

Selection

• When Ovulatory Follicles Emerge

Dominance

• Final growth of ovulatory follicles & inhibition of others

The concept of Follicular Waves

• Recruiting Follicles

Hormonal Changes

• High P4; Low E2. Tonic GnRH-> FSH
• P4 drops, Follicles and E2 rise.
• E2 rises triggering a GnRH surge, then a LH surge, leading to Ovulation

Oocyte

• Oocytes are eventually released, this leads to fertilisation

Ovulation

• Ovulation and Luteinisation of Follicle happens in the process CH-> CL-> P4

Maternal Recognition of Pregnancy:

• Involves the presence of a viable conceptus, and a PGE/PGF Balance.
• Occurs prior to the release of PGF2α (before 15 days).
• Requires the prevention of PGF from reaching the 'susceptible' CL.

Interferon Tau (IFNT)

• Previously known as bTP-1 and is a cytokine.
• Secreted from the trophoblast.
• Functions as an anti-luteolytic but is not luteotrophic.

Two-Cell, Two-Gonadotroph Theory:

• LH acts on the Theca interna/Leydig cells to convert Cholesterol to P5 and then P4, which is converted into Testosterone
• FSH acts on the Granulosa cell in order to allow aromatisation into E2
• ABP -> Sertoli cell and E2

FSH & LH Hormonal Activity

• Know and understand the hormonal activity for FSH and LH