LH Acts Primarily on Theca Cells, with Secondary Effects on Granulosa Cells
LH primarily acts on theca cells throughout follicular development, where LH receptors are constitutively present from the early follicular phase, stimulating androgen production that serves as substrate for estrogen synthesis. 1, 2
Primary Target: Theca Cells
- LH receptors are constitutively expressed on theca cells from the early follicular phase onward, making them the primary and earliest target of LH action 1
- LH stimulation of theca cells induces androgen production, which is essential for providing substrate to granulosa cells for conversion to estrogens via aromatase 1, 2
- Immunohistochemical studies demonstrate that LH receptor protein expression in theca interna cells of antral follicles is nearly twice as intense as in preantral follicles (65.4% versus 38.3%) 3
- LH can stimulate theca cells to produce amphiregulin (AREG) through the adenylate cyclase/cAMP/PKA signaling pathway 4
Secondary Target: Granulosa Cells (Mid-Follicular Phase Onward)
- Granulosa cells only begin expressing LH receptors during the mid-follicular phase, specifically when follicles reach approximately 10 mm diameter 2
- LH receptor protein first appears clearly in granulosa cells of small antral follicles, with increasing expression as follicles mature to the pre-ovulatory stage 5
- No LH receptor protein is detectable in primordial or primary follicles, with only equivocal staining in secondary follicles 5
- The capacity of LH to stimulate granulosa cells in larger follicles may be the critical mechanism for dominant follicle selection in the normal menstrual cycle 2
Clinical Implications of the Two-Cell, Two-Gonadotropin Model
- The theca-granulosa cell cooperation is essential: theca cells produce androgens under LH stimulation, which granulosa cells then convert to estrogens under FSH stimulation 1, 2
- During the follicular phase, the minimal amount of LH needed for optimal estradiol production is probably low (<1.5 IU/L plasma LH level) 1
- Western blot analysis confirms that LH receptor expression is stronger in mural granulosa cells than in cumulus cells, with cumulus cells demonstrating low but significant LH receptor protein 5
Corpus Luteum Function
- After ovulation, LH receptor protein becomes ubiquitously expressed throughout the corpus luteum, where LH is essential for maintaining progesterone production 5
- Due to LH's short half-life compared to hCG, repeated LH administration may be necessary to adequately sustain corpus luteum function, particularly following profound pituitary desensitization 1