The endocrine system maintains body homeostasis through hormone secretion, target organ responses, and feedback regulation. Hormones regulate glucose and lipid metabolism, growth and development, reproductive function, stress responses, water and electrolyte balance, bone metabolism, and energy homeostasis. They are important research objects in diabetes, thyroid diseases, reproductive endocrine disorders, adrenal diseases, and hormone-dependent tumors.

Keywords: endocrinology; hormones; insulin; thyroid hormone; steroid hormone; sex hormone; HPA axis; GPCR

1 Hormone Types and Functional Characteristics

1.1 Peptide and Protein Hormones

Peptide and protein hormones are usually secreted after precursor protein processing. They are highly water-soluble and mainly act through cell membrane receptors. Insulin, glucagon, ACTH, TSH, LH, FSH, GH, PRL, PTH, GLP-1, GIP, leptin, and adiponectin all belong to this category. These hormones often activate signaling branches such as cAMP, Ca²⁺, PI3K/AKT, MAPK, and STAT through GPCRs, receptor tyrosine kinases, or JAK/STAT-related receptors.

1.2 Steroid Hormones

Steroid hormones are derived from cholesterol and include glucocorticoids, mineralocorticoids, estrogens, progestogens, and androgens. These hormones are highly lipid-soluble and can enter cells to bind nuclear receptors or cytoplasmic receptors, thereby regulating target gene transcription. They can also produce rapid effects through non-genomic mechanisms. Steroid hormone research should focus on total hormone, free hormone, binding proteins, metabolic enzymes, and receptor expression.

1.3 Amino Acid-Derived Hormones

Thyroid hormones, catecholamines, and melatonin are amino acid-derived hormones. T3/T4 mainly regulate basal metabolism and development through thyroid hormone receptors. Epinephrine, norepinephrine, and dopamine participate in stress, cardiovascular, and neuroendocrine responses through adrenergic receptors or dopamine receptors. Melatonin is associated with circadian rhythm, sleep, and oxidative stress regulation.

1.4 Vitamin D and Local Hormone-Like Molecules

Vitamin D is metabolized by the liver and kidney to form active calcitriol, which regulates calcium-phosphate homeostasis, bone metabolism, and immune function through the vitamin D receptor (VDR). Lipid-derived molecules such as prostaglandins, leukotrienes, and endocannabinoids have local hormone-like effects and often intersect with inflammation, vascular responses, and metabolic regulation.

Table 1 Hormone Types and Functional Characteristics

2 Major Endocrine Axes and Regulatory Networks

2.1 Hypothalamic-Pituitary-Thyroid Axis

The hypothalamus secretes TRH, which promotes pituitary release of TSH. TSH acts on the thyroid gland and promotes the synthesis and release of T3/T4. Increased T3/T4 can inhibit TRH and TSH through negative feedback. This axis mainly regulates basal metabolism, body temperature, neural development, cardiovascular function, and energy expenditure.

2.2 Hypothalamic-Pituitary-Adrenal Axis

The HPA axis consists of CRH, ACTH, and cortisol, and is an important system for stress responses, glucose metabolism, and inflammatory regulation. Cortisol has a clear circadian rhythm, so sampling time must be considered during detection and interpretation. Aldosterone mainly participates in water and electrolyte balance, blood pressure regulation, and cardiac-renal remodeling.

2.3 Hypothalamic-Pituitary-Gonadal Axis

The HPG axis consists of GnRH, LH, FSH, and gonadal hormones. It regulates follicular development, ovulation, luteal function, spermatogenesis, pregnancy maintenance, and development of secondary sexual characteristics. Estrogen, progesterone, testosterone, AMH, inhibin, and prolactin are commonly used to evaluate reproductive endocrine function.

2.4 Islet-Incretin-Adipokine Network

Insulin, glucagon, GLP-1, GIP, leptin, adiponectin, and FGF21 jointly regulate blood glucose, lipid metabolism, appetite, energy expenditure, and pancreatic β-cell function. Research on diabetes, obesity, fatty liver, and metabolic syndrome usually requires simultaneous analysis of islet function, insulin sensitivity, and adipose tissue endocrine status.

2.5 Calcium-Phosphate Metabolism Axis

PTH, vitamin D, calcitonin, and FGF23 jointly regulate blood calcium, blood phosphorus, bone remodeling, and renal reabsorption. This axis is closely associated with osteoporosis, chronic kidney disease-mineral and bone disorder, parathyroid dysfunction, and vitamin D deficiency.

Table 2 Major Endocrine Axes and Detection Indicators

3 Hormone Receptors and Downstream Signaling

3.1 GPCR-Mediated Hormone Signaling

ACTH, TSH, LH, FSH, GLP-1, glucagon, PTH, catecholamines, and other hormones can act through GPCRs. GPCRs regulate branches such as cAMP/PKA, Ca²⁺/PKC, MAPK, and RhoA/ROCK through G proteins including Gs, Gi/o, Gq/11, and G12/13, thereby affecting secretion, metabolism, contraction, and cellular function.

3.2 RTK and PI3K/AKT Signaling

Insulin and IGF-1 mainly activate PI3K/AKT and MAPK branches through receptor tyrosine kinases. After insulin stimulation, p-IR, p-IRS, p-AKT, GLUT4 translocation, and glucose uptake are commonly detected to evaluate insulin sensitivity and metabolic response.

3.3 JAK/STAT-Related Hormone Signaling

GH, PRL, leptin, and related hormones regulate target gene expression through JAK/STAT-related mechanisms. GH often affects growth and metabolism through JAK2/STAT5, while leptin often affects appetite, energy expenditure, and inflammatory status through JAK2/STAT3.

3.4 Nuclear Receptor-Mediated Transcriptional Regulation

Estrogens, progesterone, androgens, glucocorticoids, mineralocorticoids, thyroid hormones, and vitamin D mainly regulate transcription through nuclear receptors. Nuclear receptor effects depend not only on hormone concentration, but also on receptor expression, coactivators, corepressors, chromatin state, and tissue context.

Table 3 Hormone Receptor Types and Research Indicators

4 Endocrine Diseases and Research Focuses

4.1 Diabetes and Metabolic Syndrome

Research on diabetes and metabolic syndrome should focus on pancreatic β-cell function, insulin resistance, hepatic glucose output, adipose tissue inflammation, and incretin function. Insulin, C-peptide, glucagon, GLP-1, GIP, leptin, and adiponectin are commonly used indicators. Increased insulin can suggest compensatory insulin resistance, but if accompanied by decreased C-peptide and hyperglycemia, it may reflect insufficient β-cell secretory capacity.

4.2 Thyroid Diseases

Thyroid diseases include hyperthyroidism, hypothyroidism, autoimmune thyroiditis, and thyroid nodule-related abnormalities. TSH, FT4, FT3, and thyroid autoantibodies are the core detection panel. Elevated TSH with decreased FT4 supports primary hypothyroidism, while decreased TSH with elevated FT4/FT3 supports hyperthyroidism. If TSH does not match peripheral hormones, pituitary factors, drug effects, or assay interference should be considered.

4.3 Reproductive Endocrine Disorders

Reproductive endocrine disorders involve polycystic ovary syndrome, decreased ovarian reserve, male hypogonadism, infertility, and abnormal pubertal development. Female sex hormone testing should specify the menstrual cycle stage. Male testosterone testing usually prioritizes morning samples and should be interpreted together with SHBG and free testosterone.

4.4 Adrenal Diseases and Stress Abnormalities

Adrenal diseases include Cushing’s syndrome, adrenal insufficiency, primary aldosteronism, and pheochromocytoma-related abnormalities. ACTH, cortisol, aldosterone, renin, and catecholamine-related indicators are strongly affected by stress, body position, medications, and sampling time, so interpretation should be combined with dynamic tests or repeated sampling.

4.5 Bone Metabolism and Calcium-Phosphate Homeostasis Abnormalities

Osteoporosis, chronic kidney disease-mineral and bone disorder, and parathyroid diseases are closely associated with PTH, vitamin D, calcitonin, FGF23, sex hormones, and thyroid hormones. Bone metabolism research should integrate blood calcium, blood phosphorus, 25(OH)D, PTH, and bone turnover markers.

Table 4 Endocrine Diseases and Common Hormone Indicators

5 Representative Products Related to Endocrinology and Hormone Research

6 Common Questions in Endocrinology and Hormone Research

6.1 Does an Increased Hormone Level Always Indicate Endocrine Hyperfunction?

Not necessarily. Increased hormone levels may result from primary hypersecretion, but may also be caused by receptor resistance, weakened negative feedback, changes in binding proteins, drug effects, or reduced clearance. Endocrine hyperfunction should be evaluated together with upstream and downstream hormones as well as target organ function.

6.2 Is a Single Hormone Measurement Sufficient to Determine the Disease Mechanism?

In most cases, it is not sufficient. Cortisol, GH, LH, FSH, sex hormones, and melatonin all show rhythmic or pulsatile secretion, so a single measurement is easily affected by sampling time. Mechanistic studies should set appropriate time points, cycle stages, or dynamic tests according to hormone characteristics.

6.3 How Should Total Hormones and Free Hormones Be Selected?

Total hormone levels include both protein-bound and free fractions, while free hormone levels are closer to the biologically active state. In studies of thyroid hormones, testosterone, cortisol, and related hormones, changes in binding proteins may affect interpretation of total hormone levels. Therefore, total or free hormone levels should be selected according to the research purpose.

6.4 What Are the Most Common Problems in Hormone Detection by ELISA?

Common problems include inappropriate sample dilution, mismatch with the standard curve range, matrix effects, interference from hemolysis or lipemia, antibody cross-reactivity, and excessive freeze-thaw cycles. For low-abundance hormone detection, sensitivity and sample handling should be given particular attention.

6.5 Does Increased Hormone Receptor Expression Indicate Enhanced Hormone Action?

Not necessarily. Increased receptor expression only indicates a change in potential responsiveness. The actual hormone effect also depends on ligand concentration, receptor activity, downstream signaling, coregulatory factors, receptor internalization, and target gene expression.

Endocrinology and hormone research should integrate hormone source, endocrine axis feedback, receptor expression, downstream signaling, and target organ function. Different hormones vary markedly in structural type, sampling time, detection method, and mechanism of action. Only by correlating hormone levels with functional endpoints can their roles in metabolism, reproduction, stress responses, bone metabolism, and hormone-dependent diseases be interpreted more accurately.

For more related articles, please see below:

[1] Endocrine system observation experiment

[2] Gonadotropins: Structural Features, Receptor Signaling, and Research and Application Frameworks

[3] Glucocorticoids: Scientific Overview and Key Application Considerations

[4] JAK-STAT Cell Signaling Pathway