Pituitary Gland Embryogenesis, Lobes and Hormones

Embryogenesis of Pituitary Gland and Tracts

• The pituitary gland begins forming in utero.
• The pituitary gland consists of two lobes.

Posterior Lobe (Neurohypophysis)

• Originates from neural tissue and is an extension of the hypothalamus.
• Axons and nerve terminals are in the posterior lobe, while the neuron cell body is in the hypothalamus.

Anterior Lobe (Adenohypophysis)

• "Adeno" means glandular.
• Originates from tissue in the roof of the mouth (epithelial cells), called Rathke's Pouch.
• The sella turcica, or Turkish saddle, is a protective cavity that surrounds the pituitary.
• Dual embryonic origins allow the pituitary gland to perform a variety of functions.

Anterior Lobe Cell Types and Hormones

• Has 5 different cell types that produce hormones.
• Somatotropes produce growth hormone (GH).
• Thyrotropes produce thyroid-stimulating hormone (TSH).
• Corticotropes produce adrenocorticotropin hormone (ACTH), which stimulates adrenal glands and cortisol release.
  • ACT stimulates, nourishes, and acts favorably.
• Lactotropes produce prolactin.
• Gonadotropes produce luteinizing hormone (LH) and follicle-stimulating hormone (FSH) which are gonadotropes,.

Posterior Lobe

• Does not produce hormones, but can store them, such as oxytocin and ADH made in the hypothalamus.

Sexual Differentiation of Reproductive Tracts

• Occurs in utero.
• XX chromosomes indicate female, while XY chromosomes indicate male.

Primordial Germ Cells

• Originate in the hindgut and migrate to the gonadal ridge.
• The reproductive and renal systems develop at the same place and time in the embryo.

Mesonephric Ducts

• Also called Wolffian ducts and develop into the epididymis/ductus deferens.

Paramesonephric Ducts

• Also called Müllerian ducts which turn into oviducts, uterus, cervix, and vagina.

SRY Gene

• The sex-determining gene is located on the Y chromosome.
• SRY protein stimulates the development of the male system and the production of anti-Müllerian hormone (AMH).
• Sertoli cells make anti-Müllerian hormone.
• It also drives the production of androgens, which further stimulates the development of the male reproductive tract.

Abnormalities of Development

• Cryptorchidism is the failure of testes to descend into the scrotum.
• Inguinal herniation occurs when a portion of the testes passes through the inguinal canal.
• Free martin occurs when a heifer is born twin to a bull.

Regulation of Reproduction

• The nervous and endocrine systems work together to control reproduction.
• Neural control involves neurons.
• Neurons translate stimuli into neural signals that alter reproductive functions.

Simple Neural Reflex

• Involves direct innervation of a target tissue.
• Neurotransmitters are involved.
• An example is the scrotum changing due to temperature.

Neuroendocrine Reflex

• Uses neurohormones to affect target tissue.
• Hormones are made and enter the blood before reaching the target tissue.
• There is no direct innervation of the target tissue.

Hypothalamus

• It is a neural control center for reproduction, a small ventral area of the brain made up of clusters of neuronal cell bodies.
• Responds to a variety of external and internal stimuli.

Hypothalamus Communication

• The hypothalamus communicates with the posterior pituitary via direct innervation.

Hypothalamo-Hypophyseal Portal System

• A special capillary system for the hypothalamus to communicate with the anterior pituitary.
• Minute amounts of hormones from the hypothalamus act on the anterior pituitary.
• The hypothalamus makes "releasing hormones," such as GnRH (gonadotropin-releasing hormone).

Endocrinology

• Relies on hormones to cause a biological effect.
• A hormone is a substance produced by a tissue that travels in blood to bring about a change in a target tissue.

Characteristics of Hormones:

• Active in small quantities, i.e., 1g of P4/1 mL of blood = 1:1 ratio.
• Levels in pregnant females (P4): 1 pg/mL = 1:1,000,000,000,000.
• The concentration of most hormones in blood is low.

Hormone Action

• Carried in blood and have autocrine and paracrine effects.
• Act on target tissues.
• Hormone (H) binds to a hormone receptor (HR).

Physiological Activity of Hormones

• This depends on the half-life of the hormone (t1/2), receptor density on the target tissue, hormone receptor affinity, and secretion patterns of hormones.

HPG Axis

• The (hypothalamo-pituitary-gonadal) Axis is the primary axis of hormone control
• The hypothalamus secretes releasing hormones like GnRH.
• The pituitary gland secretes hormones, affecting the gonads.
• The gonads secrete hormones (sex steroids), like E2 and P4.

Negative Feedback of HPG Axis

• Sex steroids can suppress the GNRH hormones causing negative feedback.

Positive Feedback of HPG Axis

• Stimulation of GnRH neurons increases GnRH secretion causing positive feedback.
• Peak E2 production stimulates GnRH neurons to increase LH, resulting in LH surge.
• Negative feedback results in suppression of GnRH neurons.
• Positive feedback results in stimulation of GnRH neurons.

Hormone Classification

• Classified in different ways through biochemical classification.
• Two types including amino acid-based hormones and steroids.

Amino Acid-Based Hormones

• Protein hormones are made of many amino acids.
• Peptide hormones are small numbers of amino acids joined together.
• Glycoproteins have many amino acids joined together plus sugars.

Steroids

• All steroids come from cholesterol (27C).
• Cholesterol is the starting molecule for steroids.

Cholesterol Synthesis in the Liver

• HMG-CoA reductase is the rate-limiting enzyme in cholesterol synthesis.
• Drugs like Lipitor (statins) inhibit this enzyme.

Transport of Cholesterol

• Cholesterol is transported by transport proteins.
• HDL (high-density lipoprotein)
• LDL (low-density lipoprotein)

Modified Fatty Acids

• For example, prostaglandins, where the precursor is arachidonic acid.

Steroid Synthesis (Steroidogenesis)

• Mitochondria make and contain enzymes called cytochrome P450.
• SER (smooth endoplasmic reticulum).
• 3BHSD -- 3 Beta Hydroxy steroid Dehydrogenase.
• Aromatase converts androgens to estrogens.

Sources of Steroids

• Gonads, adrenal glands, and placenta.

Characteristics of Steroids

• All are made from cholesterol.
• Small molecular weight.
• Fat-loving (lipophilic) or H2O-hating (hydrophobic).
• Synthesis and secretion are tightly coupled.
• Steroids are not stored.
• Active when given orally or intramuscularly.
• Not species-specific.

Characteristics of Protein Hormones

• All are made with amino acids hooked together.
• Most are made and stored.
• Must be injected (cannot be given orally).

Modified Fatty Acids

• DGF2 and PGE2 are the main ones for reproduction.
• Arachidonic acids precursor for prostaglandins.

Cox-2

• Cox-2 is the rate-limiting enzyme for making prostaglandins.
• Aspirin, ibuprofen, and Banamine inhibit Cox-2.

Hypothalamic Hormones

• The source is the hypothalamus.

GnRH (Gonadotropin-Releasing Hormone)

• A peptide (10-AA in length).
• Functions in males and females include stimulating production and release of gonadotropins (LH and FSH).

Corticotropin-Releasing Hormone

• In males and females, stimulates synthesis and release of ACTH a peptide.

GHRH (Growth Hormone-Releasing Hormone)

• In both males and females, it stimulates the synthesis and releases GH; a peptide.

Oxytocin

• Also made by corpus luteum.
• A small peptide.
• In both males and females, stimulates contractions.
• In females only, induces milk letdown, contractions at birth (myometrium), and maternal behavior.
• Pitocin is a synthetic version.

Pituitary Hormones that Act on the Anterior Lobe

• FSH (Follicle Stimulating Hormone).
• LH (Luteinizing Hormone).
• Prolactin.
• Adrenocorticotropin (ACTH).

FSH (Follicle-Stimulating Hormone)

• Glycoprotein from anterior pituitary (gonadotropes).

Functions

• In males, stimulates Sertoli cells to stimulate inhibin and ABP production.
• In females, stimulates follicular growth producing inhibin and estradiol.

LH (Luteinizing Hormone)

• Glycoprotein from anterior pituitary (gonadotropin).

Functions

• In males, stimulates androgen production and release.
• In females only, LH is paramount for ovulation (LH surge), stimulates CL formation and maintenance and stimulates P4 release.
• Considered a luteotropic hormone.
• LH, FSH, and TSH all share a beta subunit that provides hormone specificity.

Prolactin

• Protein from anterior pituitary (lactotropins).
• In females only, stimulates lactogenesis, maternal behavior, mammary gland development, and acts like GH.

Adrenocorticotropin (ACTH)

• Anterior Pituitary (corticotropes) and it functions in both males and females.
• Stimulates synthesis and release of glucocorticotropin (cortisol).

Gonadal Hormones

• Estrogens (family of steroids) which is Estradiol 17B (most biologically active).

Source

• Ovaries (granulosa cells).
• Placenta.
• Testis.

Functions

• Drives female into estrus (heat).
• Stimulates female tract secretions.
• Stimulates contractions of the female tract.
• Drives 2ndary sex characteristics.
• Increases the Growth of tract and mammary glands.
• Increases calcium uptake and ossification of bone and protein anabolic effects.

Progesterone

• Is a steroid and the P4 source is CL and placenta.
• Functions include maintaining pregnancy and suppress GnRH release
• Negative feedback.
• Stimulates reproductive tract secretions like histotroph secretions.
• Stimulates cervical secretions (thick, viscous mucus).
• Blocks uterine myometrial contractions and increases final alveolar development in mammary glands.

Androgens (family of steroids)

• Include testosterone and dihydrotestosterone (DHT).
• Source is the gonads (Leydig cells and theca cells in female).

Functions

• Stimulate anabolic growth, are essential for spermatogenesis, drives male sexual behavior
• Stimulates accessory sex glands.
• Increases 2ndary sex characteristics.

Inhibin (glycoprotein)

• From granulosa cells in females and Sertoli cells in males which suppresses FSH release.
• Relaxin (protein) source is CL and placenta and which also helps with softening connective tissue in the cervix,.
• Increases elasticity of the pelvic ligament and cervical dilation.
• PGE2 is a modified fatty acid

PGE2

• Modified fatty acid witha source in females as uterus, ovary, and corpus luteum and in males, vesicular glands.

Functions

• Vasodilation, helps with ovulation, stimulates CL formation.
• PGF2alpha (modified fatty acid) are sourced from the uterus (endometrium), CL, and accessory sex glands.
  • Females which initiates luteolysis.
  • Increases uterine contracts and helps w/ ovulation.

Functions

• ↑ contractions of cauda epididymis.
• Placental Lactogen (CSH).
• Protein and source is placenta which increases lactation and fetal growth.
• hCG = human chorionic gonadotropin
• Glycoprotein
  • Source placenta (chorion layer) which is the fetal component and it increases the P4 production and release.
• Has luteotropic/LH-like properties.
• The nCG has a long T1/2 (half-life of ~72 hours or 3 days.
• NCG is measured by human pregnancy tests.

Equine Chorionic Gonadotropin(eCG)

• It is a glycoprotein that is sourced from the placenta.
• eCG has a long T1/2 where eCE-acts like FSH in non equine species.
• Functions in mares as it causes formation of Accessory Glands.

Herferon Tau (IFNy)

• Source is trophoblast cells (Placenta), Protein-specific in ruminants.
• Function in maternal recognition of Pregnancy.