Classification of hormone receptor locations:

• Androgens are lipophilic steroid hormones that readily diffuse across the plasma membrane and bind intracellular androgen receptors (AR) in the cytoplasm/nucleus.
• Estrogens are lipophilic steroid hormones that bind intracellular estrogen receptors (ER$\alpha$/ER$\beta$).
• Progestins (progesterone) are lipophilic steroid hormones that bind intracellular progesterone receptors (PR) to modulate transcription.
• Insulin is a large peptide hormone that cannot cross the hydrophobic lipid bilayer; it binds an extracellular cell-surface receptor tyrosine kinase (RTK).

Hypothalamic control of appetite and energy homeostasis:

• Glucagon acts primarily on hepatic glycogenolysis and gluconeogenesis.
• Adiponectin promotes fatty acid oxidation and insulin sensitivity primarily in muscle and liver.
• Ghrelin binds GHSR on NPY/AgRP neurons to stimulate NPY release and promote hunger.
• Circulating insulin (along with leptin) crosses the blood-brain barrier to bind insulin receptors on orexigenic NPY/AgRP neurons in the arcuate nucleus of the hypothalamus, hyperpolarizing them and inhibiting the expression and release of orexigenic neuropeptide Y (NPY), thereby suppressing appetite as an anorexigenic signal.

Historic discovery of insulin:

• Frederick Banting and John J.R. Macleod were jointly awarded the 1923 Nobel Prize in Physiology or Medicine for the discovery and isolation of insulin at the University of Toronto (Banting shared his prize money with Charles Best, and Macleod shared his with James Collip).
• Josef von Mering showed diabetes after pancreatectomy with Minkowski in 1889.
• Thompson was an early insulin trial patient, not a co-laureate.
• Oskar Minkowski demonstrated the endocrine role of the pancreas in 1889.

Hypothalamic-pituitary-thyroid axis dynamics:

• Statement (I) is correct: Hypothyroidism is by definition the clinical and biochemical state resulting from insufficient production and secretion of thyroid hormones ($T_4$ and $T_3$) by the thyroid gland.
• Statement (II) is incorrect: In primary hypothyroidism (which constitutes $\gt 95\%$ of clinical cases in animals), circulating levels of free $T_4$ and $T_3$ are low, which relieves negative feedback inhibition on the anterior pituitary gland; consequently, the pituitary secretes markedly elevated (above normal) concentrations of Thyroid-Stimulating Hormone (TSH) in an attempt to stimulate the failing thyroid gland.