Endocrine Signaling Types

• Notes on endocrine pathology lecture 1 by Diana Bochynska.

Endocrine Signaling

• In endocrine signaling, a signaling molecule, like a hormone, is transported in a vesicle.
• Endocrine signals travel through the circulatory system to reach distant target cells with appropriate receptors.
• Thyroid-stimulating hormone is an example.

Autocrine Signaling

• Receptors are on the plasma membrane of the same type of cell that releases the signaling molecules.
• Interleukin-1 is an example in Monocytes.

Paracrine Signaling

• Receptors occur on different target cells located near the signaling molecule-secreting cells.
• The fibroblast growth factor family is an example.

Intracrine Signaling

• Receptors occur on the nuclear envelope of the cell that synthesized or internalized the signaling molecules.
• Steroid hormones are an example.

Pituitary Gland Location

• The pituitary gland (adenohypophysis [anterior pituitary gland] and neurohypophysis [posterior pituitary gland]) is ventral to the hypothalamus and caudal to the optic chiasm.
• It has two main parts: the anterior pituitary (adenohypophysis or AP) and the posterior pituitary (neurohypophysis or PP).
• The anterior pituitary envelopes the posterior pituitary.

Anterior Pituitary

• Derived from epithelium/ectoderm of oral cavity/pharynx and has 3 parts.
• The pars distalis is a part of the anterior pituitary.
• The pars tuberalis is a tube-like structure around the infundibulum.
• The pars intermedia (POMC) lies between the neurohypophysis and pars distalis.
• The hypophyseal cavity/cleft is a remnant of Rathke's pouch.

Pars Distalis Cells

• Cells are classified as acidophils, basophils, or chromophobes.
• Each cell type, called a "-troph," expresses a peptide, protein, or glycoprotein hormone termed a tropin representing definitive and terminal differentiation.

Pars Intermedia

• Varies between species.
• Melanotrophs are the most abundant cell type, secreting melanocyte-stimulating hormone and lipotropin.
• These peptide hormones are processed products of POMC expressed by the melanotrophs.

Pars Tuberalis

• Cells have melatonin receptors and are believed to regulate the seasonal reproductive cycle in some domesticated mammals.

Neurohypophysis

• The posterior pituitary is derived from neuroectoderm.
• It has two parts: the pars nervosa and the infundibulum.
• Hormones made in the hypothalamus, such as antidiuretic hormone (ADH) and oxytocin, are stored here for direct release into the blood stream.

Pituitary Gland Diseased in Dogs & Cats

• Pituitary abnormalities occurred in 26.4% of dogs and 15.3% of cats.
• Cystic changes are the most common lesion.
• Pituitary neoplasia was detected in 14.1% of middle-aged and old dogs.

Adenohypophysis Disorder

• Inflammation can occur hematogenously, as the blood-brain barrier does not protect the hypophysis.
• Inflammation can extend from adjacent tissues like the meninges, brain, or pharynx.
• Lymphoplasmacytic hypophysitis may be immune-mediated and observed in the canine pituitary gland; less common than similar processes in the thyroid or adrenal glands.

Hypopituitarism Lesions

• Pituitary cysts can form.

Pituitary Dwarfism

• Clinical signs include:
  • Slower growth, retention of puppy hair.
  • Bilaterally symmetrical alopecia that progresses to near-complete alopecia.
  • Small tufts of hair remain on the legs and head.
  • Thin and scaly skin with hyperpigmentation and comedones.
  • Delayed physeal closure
  • Infantile external genitalia
  • Delay or absence of permanent dentition are some characteristics.

Hypersomatotropism

• Acromegaly occurs in cats.
• There is adenoma or adenomatous hyperplasia of adenohypophyseal (anterior pituitary) somatotrophs.
• Growth hormone promotes growth of soft and bony tissues.
• There is decreased insulin insensitivity, increased lipolysis, increased protein synthesis, increased hepatocellular synthesis, and secretion of IGF-1.
• Large stature with broad facial features, inferior prognathism, and enlarged feet, renomegaly, hepatomegaly, and myocardial hypertrophy can manifest.
• In dogs, it is usually caused by chronic GH secretion from hyperplasia of mammary tissue resulting from endogenous (diestrus) or exogenous progestins.
• Pituitary adenomas are a rare cause, similar to humans and cats.

Brain Tumors in Horses

• Grossly, the tumors are well-circumscribed, partially encapsulated, multinodular, space-occupying lesions that tend to expand, and subsequently compress the hypothalamus.

Pituitary Pars Intermedia Dysfunction (PPID)

• PPID is "Equine Cushing's".
• Non-productive pituitary adenomas can form.
• Clinical signs:
  • Hirsuitism (failure to shed).
  • PU/PD.
  • Polyphagia.
  • Hyperhidrosis.
  • Insulin resistance.
  • Abnormal fat deposition.
• In Cushing’s disease, pars intermedia melanotrophs do not express glucocorticoid receptors and are controlled instead by dopaminergic inhibition from hypothalamic neurons.
• In autumn, shortened daylight decreases dopaminergic inhibition -> increased activity of the pars intermedia promotes hair growth and increased adipose tissue deposition (to prepare for winter).
• In PPID, pars intermedia dopamine concentrations are decreased year-round, synthesising excessive pro-opiomelanocortins (POMC), secreting excessive a-MSH, β-endorphins, and corticotrophin-like intermediate peptide (CLIP).
• Clinical signs in the horse with pars intermedia adenoma:
  • Result from hypothalamic or neurohypophyseal dysfunction due to compression of the hypothalamus.
  • Over production of beta-endorphin => unresponsive to pain, docile nature.
  • Compression of hypothalamus => hirsutism, polyphagia, hyperpyrexia.
• Compression of neurohypophysis and decreased ADH secretion => polyuria.
• The adrenal glands of horses with PPID are usually unremarkable.

Equine Metabolic Syndrome

• Physically inactive horses consuming high-energy rations, especially those with a high glycemic index (grass is a major dietary source of sugars), are susceptible.
• Ponies and miniature horses are at risk.
• Obesity, hypertriglyceridemia, and hyperleptinemia can occur.
• Insulin resistance is often detected when hyperinsulinemia is screened as an indicator.
• Type 2 diabetes mellitus is seldom diagnosed in horses.
• Chronic "endocrinopathic" laminitis.

Laminitis

• In horses with PPID, laminitis can occur due to co-existing hyperinsulinemia.
• Of 325 horses with PPID, 32% had basal, non-fasting hyperinsulinemia, and of those, 66% had laminitis.
• Laminitis has been experimentally induced via insulin administration.
• Hemidesmosome, a vital basement membrane component, loses density due to hyperinsulinemia.
• Reduced density results in widening, damage, weakening of basement membrane, and lamellar failure.

Ruminants Disorders

• Adenohypophyseal aplasia and prolonged gestation can occur.
• There can be aplasia of the adenohypophysis with normal development of the neurohypophysis.
• A genetic disease may occur in Guernsey and Jersey cattle.
• The pituitary gland can fail to develop due to hypothalamic malformations (e.g., from ingestion of Veratrum californicum by pregnant ewes).
• Defective adenohypophyseal ACTH secretion in ruminant fetuses affects adrenal cortices subnormally, resulting in inadequate cortisol synthesis and secretion.

Follicular Hyperplasia

• Goiter: Nonneoplastic thyroid enlargement.
• It is an enlargement of the thyroid gland from follicular cell hyperplasia. This may or may not always be grossly visible.
• Causes: Iodine deficiency/excess, goitrogens, thyroid hormone synthesis defects.
• Types: Diffuse (throughout the gland) or multinodular.
• Diffuse goiter: TSH-induced compensatory response to hypothyroidism (low T3/T4).
• Multinodular goiter: autonomously functioning hyperplastic cells causing hyperthyroidism; unaffected cells atrophy due to low TSH.

Hyperplastic Goiter

• It is due to iodine deficiency.
• Without sufficient iodine, inadequate T4/T3 synthesis leads to the creation.
• The thyroid becomes diffusely enlarged and reddened due to increased vascularity.

Colloid Goiter

• Is the involution of hyperplastic goiter.
• Hyperplastic thyroid produces sufficient T4 and T3 when iodine deficiency is corrected or postnatal thyroid hormone demand decreases,
• Negative feedback reduces TSH secretion.
• Consequently, the goiter involutes to colloid goiter, remaining enlarged but becoming pale brown with decreased vascularity and a translucent appearance due to colloid-distended follicles.

Iodine Deficiency

• Without sufficient iodine, deficient synthesis of T4 and T3 results in TSH-induced hyperplastic goiter.
• Iodine-deficient fetuses and neonates experiencing a robust TSH response also show extrathyroidal lesions such as myxedema.
• They have an accumulation of glycosaminoglycans and water in the dermis and subcutis, or less hair or wool than expected.

Excessive TSH

• Increased TSH is needed to achieve hyperplasia when T4 is low and feedback inhibition is lost.

Decreased T4 Increases TSH

• This can be caused by:
  • Iodine deficient diet.
  • Goiterogenic substances - interfere with production of T4/TG.
  • Congenital dyshormonogenic goiter - autosomal recessive defects in enzymes.
  • Excess dietary iodide.

Animals With Excess Iodine

• The thyroid acutely inhibits the organification of iodine, by a mechanism not well understood.
• The Wolff-Chaikoff effect effectively rejects large iodide quantities in an attempt to prevent the thyroid from synthesizing large amounts of thyroid hormones.
• The acute Wolff-Chaikoff effect lasts for a few days, but organification resumes due to "escape".
• **
• Disclaimer: These notes are for informational purposes only and should not be considered a substitute for professional veterinary medical advice. I am an AI chatbot and cannot provide diagnoses or treatment recommendations.*