Hormone Regulation and Function

Hormone Regulation

• Serotonin controls sleep, pain control, sexual behavior, and hormone secretion in seasonally breeding mammals.

Hormone Activity

• Lipid-soluble hormones (thyroid and steroid hormones) have intracellular receptors, alter gene expression, and turn specific genes on or off.
• Water-soluble hormones (eicosanoids, polypeptide, and amine) have receptors as integral transmembrane proteins on the plasma membrane, using signal transduction.

Signal Transduction

• Steps:
  • Hormone (first messenger) activates membrane G-protein.
  • Adenylyl cyclase is activated, turning ATP into cAMP (second messenger).
  • cAMP activates a protein kinase.
  • The kinase phosphorylates a protein, activating or inactivating it.
  • Phosphodiesterase inactivates cAMP if no more hormones bind to their extracellular receptors.

Gonadogenesis

Stage of Indifferent Gonads

• Gonads develop from mesenchyma, coelomic epithelium, and Primordial Germ Cells.
• Genital Ridge formation: genital ridges are formed at the 5th week of development by the proliferation of mesenchyme covered by coelomic epithelium.

Germ Cell Migration to Genital Ridges

• Primordial Germ Cells (PGCs) gather at the allantois, then pass into the yolk duct, the intestine, the dorsal mesentery, and finally reach the genital ridges.

Sex Cords Formation

• Sex cords (vascularized) are formed by a second group of cells deriving from the coelomic epithelium, which moves and surrounds the PGCs.

Chromosomal-Genetic Sexual Dimorphism

• X and Y chromosomes, with Y chromosome dominance.

Reproductive Messengers

Mode of Secretion

• Secretory process depends on the nature of secretion, blood supply of the secreting tissue, and solubility of the hormone (water-soluble or lipid-soluble).
• Endocrine: mediators are secreted into the interstitial fluid, then diffuse into blood capillaries, and circulate until they reach the target cells.

Classification of Hormones

Lipids

• Steroids and Eicosanoids, often carried on transporters.
• Steroids:
  • Derived from cholesterol, which is synthesized from acetate.
  • Cholesterol is converted to pregnenolone in the inner mitochondrial membrane.
  • Pregnenolone is converted to sex steroids in the smooth ER.
  • Four main families of steroids: progestagens, androgens, oestrogens, and corticosteroids.
  • Biosynthetic unit enzymes interconvert them.
• Eicosanoids:
  • Water-soluble, needing transporters to cross the plasma membrane.
  • Comprise Prostaglandins and Leukotrines, with PGs having a greater role in reproductive processes.
  • Arachidonic acid is a main precursor for PGs.

Functions of Testosterone

• Activation of hypophyseal testicular axis
• Differentiation of male genital organs
• Masculinization of urogenital sinus and external genitalia
• Acquisition of secondary sex characteristics and male behavior
• Maintenance and integrity of germ line (along with FSH)
• Initiation and maintenance of spermatogenesis

Control of Testicular Functions

Neuro-Endocrine Control

• The hypothalamo-hypophyseal axis regulates the reproductive system.
• GnRH released by the hypothalamus forms a blood vascularization with capillaries of the portal system, allowing rapid hormone transfer.
• GnRH controls the expression of LH and FSH, which have a pulsatile mode of release.

Functions of LH and FSH

• LH: acts on Leydig cells, stimulating production of testosterone from cholesterol.
• Testosterone: binds to intracellular receptors on Sertoli cells, stimulating them to secrete ABP.
• FSH: binds to extracellular receptors on Sertoli cells, stimulating RNA synthesis, testicular fluid production, and protein synthesis (including inhibin and ABP).

Negative Feedback Regulation

• Testosterone has a negative feedback on GnRH, inhibiting the secretion of LH and FSH.
• Inhibin: produced by Sertoli cells, inhibits the secretion of FSH by negative feedback.