Reproductive hormones

What is a hormone?

Definition of hormone Hormone –Greek “I excite” or “I arouse” First used by Starling in 1895 –Classical definition Chemical signals that travel via bloodstream to affect the function of the distant organ –Regulatory factor Secretory organ Target organ/tissue

Definition of hormone Hormones –Contemporary definition Much broader Local factors (produced and used without being carried in the bloodstream) –Autocrine (produced and used by the same cell/tissue) –Paracrine (produced by the neighboring cells and transported via the interstitial fluid)

LH FSH Estradiol Hypothalamus Pituitary gland GnRH Ovary

Antrum Granulosa cells Theca interna Theca externa Basement membrane Oocyte

Granulosa cells (GC) Theca cells (TC) Basement membrane

Classes of hormones Three general classes –Lipids Cholesterol derivatives (steroids) 12-C fatty acid derivatives (eicosanoids) –Proteins and polypeptides –Monoamines

Cholesterol and its derivatives Cholesterol –Large molecule Hydrocarbon ring –Highly hydrophobic –Source Diet De Novo synthesis –Found in cell membrane

Cholesterol and its derivatives Derivatives –Vitamin D –Bile acid Lipid digestion –Steroid hormones Sex steroids Adrenal steroild –All cholesterol derivatives contain sterol ring

Steroid hormones Commonly called sex steroid hormones –Produced mainly by the gonads Ovaries and testis Some production by placenta, adrenal gland, and brain –Water-insoluble but lipid soluble Easily move across the plasma membrane Bound to Steroid hormone-binging globulin during transport

Three classes of sex steroid hormones –Progestin/progestagens –Estrogens –Androgens Produced through metabolic process –Steroidogenesis

Steroidogenesis Source of cholesterol –Acetate De Novo Synthesis –Lipoproteins HDL (humans and rodents) LDL (cattle) Common pathway –Conversion of cholesterol to pregnenolone

Splits into two different pathway with the same outcome –Delta-4 pathway Conversion of pregnenolone to progesterone Conversion of progesterone to androstenedione –Delta-5 pathway Conversion of pregnenolone to androstenedione

Production of estrogens –Final destination of steroidogenesis in the ovary Conversion of androgens (testosterone) to estradiol-17 beta –Some species (i.e. rats) use delta-4 pathway, whereas others (i.e. cows) prefer delta-5 pathway

General function of steroid hormones Development of physical characteristics –Male and female sex characteristics Primary (reproductive organs) Secondary (physical) Reproductive success –Sexual behavior and libido –Fertility –Pregnancy

Eicosanoids Derivative of 12-C fatty acid (Arachidonic acid) –Prostaglandins (more important for reproduction) –Leukotriens Arachidonic acid released from phospholipid component of the cell membrane –Phospolipase A –Phospholipase C

Prostaglandins –Produced from leukotriens through cyclooxygenases –No specific organ of production Originally isolated from prostate gland Many reproductive organs produce prostaglandins –Quickly metabolized Lungs

Protein hormones Three subclasses –Glycoproteins –Proteins Growth hormone Prolactin Placental lactogens –Cytokines (immune system) –Polypeptdes

Glycoproteins Produced by the anterior pituitary –Gonadotropins Follicle-stimulating hormone (FSH) Luteininzing hormone (LH) –Thyroid-stimulating hormone (TSH) Less important for regulation of gonadal function Produced by placenta –Chorionic gonadotropins (CG) Human (hCG) Horse (eCG/PMSG)

Structural similarity –Two subunits Alpha –Universal Beta –Unique to each hormone Linked together non-covalently (disulfide bridges) –Glycosylated Attachment of carbohydrate moiety onto the subunits –Unique among hormones

Proteins Pituitary hormones –Growth hormone (GH) –Prolactin (PRL) Placental hormones –Unique to humans, rodents, and ruminants Placental lactogen (PL) GH-Variant (GH-V) Affect metabolism and lactation Affect ovarian functions

Cytokines Different from hormones –No specific organ/cells produce Immune response Inflammation –Multiple targets –Interactions to modulate activities of other cytokines –Redundant functions –Auto/paracrine factor rather than endocrine factor

Ovarian proteins –Inhibins –Activins –Mullerian inhibitory substance/hormone (MIS) –Two subunits (alpha and beta) Different combination determines the nature of proteins

Polypeptides Small proteins –Short in length compared to proteins –Produced by cleaving large preprohormone peptides

Hypothalamic neuropeptides –Gonadotropin- releasing hormone (GnRH) Regulates secretion of LH and FSH Composed of 10 amino acids

Posterior pituitary hormones –Oxytocin Composed of 9 amino acids Produced by the neurons within the hypothalamus but secreted by the posterior pituitary gland Induces contraction of smooth muscles Critical for milk let-down