Luteinizing Hormone (LH) Controls Testosterone Production
Luteinizing hormone (LH), secreted by the anterior pituitary gland, is the primary pituitary hormone that directly regulates testosterone synthesis in the testicular Leydig cells. 1, 2
Mechanism of LH-Mediated Testosterone Control
LH binds specifically to LH receptors on the plasma membrane of testicular Leydig cells, triggering intracellular signaling cascades that stimulate testosterone production 2
The LH receptor activates the adenylyl cyclase signaling system, which includes Gs-protein and the enzyme adenylyl cyclase that catalyzes cAMP synthesis, ultimately driving steroidogenic enzyme activity 2
Most testosterone in men is produced in the testes in response to LH, with serum testosterone falling to castrate levels (≤10 ng/mL) after removal of LH stimulation through bilateral orchiectomy 1
LH is the central regulatory molecule controlling both steroidogenesis and Leydig cell cholesterol homeostasis, as demonstrated in animal models where LH upregulates genes involved in both cholesterol biosynthesis/uptake and steroid biosynthesis 3
The Hypothalamic-Pituitary-Gonadal Axis
The hypothalamus secretes LHRH (luteinizing hormone-releasing hormone), which stimulates the anterior pituitary to release LH, creating a three-component feedback network with testosterone 4
Testosterone exerts negative feedback on both the hypothalamus and pituitary, suppressing LHRH and LH secretion to maintain hormonal homeostasis 5, 6
This feedback loop explains why exogenous testosterone completely suppresses spermatogenesis—it shuts down endogenous LH production, eliminating the signal for testicular testosterone synthesis and sperm production 6
Role of FSH (Secondary Consideration)
Follicle-stimulating hormone (FSH) primarily targets Sertoli cells rather than directly stimulating testosterone production 7
FSH influences Leydig cell response to LH indirectly, contributing to overall testicular function but not serving as the primary driver of testosterone synthesis 7
In infant testicular cell cultures, FSH stimulation can increase testosterone secretion through paracrine factors secreted by Sertoli cells, suggesting indirect regulatory mechanisms during early development 8
Clinical Implications
LHRH agonists (like leuprolide) initially stimulate LH release, causing a testosterone "flare" for 2-3 weeks, before downregulating pituitary LH receptors and achieving medical castration 1
Human chorionic gonadotropin (hCG) acts virtually identically to pituitary LH, stimulating testosterone production by testicular Leydig cells, which is why it can be used therapeutically in secondary hypogonadism while preserving fertility 1, 5
Elevated LH with low testosterone indicates primary testicular failure (the pituitary is maximally stimulating but the testes cannot respond), while low LH with low testosterone indicates secondary (pituitary/hypothalamic) hypogonadism 6