The Hypothalamic-Pituitary-Gonadal axis regulates reproduction and sex hormone production through GnRH (gonadotropin-releasing hormone), LH/FSH (luteinizing hormone/follicle-stimulating hormone), and sex steroids (oestrogen, Progesterone, Testosterone).
graph TD
PULSE["Pulsatile signal<br/>(GnRH pulse frequency<br/>determines LH vs FSH)"] --> GnRH
subgraph "Hypothalamus"
GnRH["GnRH neurons<br/>gonadotropin-releasing<br/>hormone"]
end
subgraph "Anterior Pituitary"
GnRH -->|"stimulates"| LH["LH<br/>luteinising hormone"]
GnRH -->|"stimulates"| FSH["FSH<br/>follicle-stimulating<br/>hormone"]
end
subgraph "Female Gonads"
FSH -->|"promotes"| FOLL["Follicle development<br/>+ oestrogen production"]
LH -->|"triggers"| OVUL["Ovulation +<br/>progesterone from<br/>corpus luteum"]
end
subgraph "Male Gonads"
LH -->|"stimulates"| LEYDIG["Leydig cells<br/>→ testosterone"]
FSH -->|"promotes"| SERT["Sertoli cells<br/>→ spermatogenesis"]
end
FOLL --> SEX_F["Oestrogen<br/>Progesterone"]
OVUL --> SEX_F
LEYDIG --> SEX_M["Testosterone"]
SEX_F -.->|"negative feedback<br/>(+ positive at mid-cycle)"| GnRH
SEX_F -.->|"negative feedback"| LH
SEX_M -.->|"negative feedback"| GnRH
SEX_M -.->|"negative feedback"| LH
SEX_F --> EFF1["Immune modulation<br/>Pain sensitivity<br/>Metabolic effects"]
SEX_M --> EFF2["Body composition<br/>Insulin sensitivity<br/>Immune effects"]
style PULSE fill:#f8d7da,stroke:#dc3545
style GnRH fill:#cce5ff,stroke:#004085
style LH fill:#cce5ff,stroke:#004085
style FSH fill:#cce5ff,stroke:#004085
style FOLL fill:#fff3cd,stroke:#ffc107
style OVUL fill:#fff3cd,stroke:#ffc107
style LEYDIG fill:#fff3cd,stroke:#ffc107
style SERT fill:#fff3cd,stroke:#ffc107
style SEX_F fill:#d4edda,stroke:#28a745
style SEX_M fill:#d4edda,stroke:#28a745
style EFF1 fill:#cce5ff,stroke:#004085
style EFF2 fill:#cce5ff,stroke:#004085
¶ HPG suppression by stress and inflammation
graph LR
STRESS["Chronic stress<br/>HPA activation"] --> SUPP["GnRH suppression"]
INFLAM["Metabolic dysfunction<br/>inflammation"] --> SUPP
SUPP --> LOW["Low LH / FSH"]
LOW --> HYPO["Hypogonadism<br/>infertility<br/>amenorrhoea"]
HYPO --> META["Altered body composition<br/>insulin resistance<br/>immune dysregulation"]
META -.->|"perpetuates"| INFLAM
style STRESS fill:#f8d7da,stroke:#dc3545
style INFLAM fill:#f8d7da,stroke:#dc3545
style SUPP fill:#fff3cd,stroke:#ffc107
style HYPO fill:#f8d7da,stroke:#dc3545
style META fill:#cce5ff,stroke:#004085
style LOW fill:#fff3cd,stroke:#ffc107
Hypothalamic GnRH neurons release GnRH in pulsatile fashion. GnRH stimulates anterior pituitary to secrete LH and FSH. In females: FSH promotes follicle development and oestrogen production; LH triggers ovulation and Progesterone production from corpus luteum. In males: LH stimulates Testosterone from Leydig cells; FSH promotes spermatogenesis in Sertoli cells. Sex steroids provide negative feedback (and positive feedback at mid-cycle in females).
HPG axis is highly sensitive to metabolic stress, inflammation, and HPA activation. chronic stress and metabolic dysfunction suppress reproduction. Sex Hormones significantly influence immune, inflammation, pain sensitivity, and metabolic health, with major male-female differences in disease susceptibility.
- Exhibits significant sexual dimorphism in structure and function
- Suppressed by chronic HPA axis activation (stress inhibits reproduction)
- Requires adequate adipose tissue and metabolic health for normal function
- GnRH pulse frequency determines LH vs FSH predominance
- Female cycle creates fluctuating immune and metabolic states
- Metabolic repercussions include effects on body composition, Insulin sensitivity