Concentrations of progesterone and 17-hydroxy progesterone in human follicular fluid and serum reflecting their production in granulosa - and theca cells

Research Question How is the production of progesterone (P4) and 17-hydroxy-P4 (17-OH-P4) regulated between theca (TCs) and granulosa cells (GCs) during the follicular phase, during ovulation and after transformation into a corpus luteum? Design Three cohorts were examined: 1) 31 women undergoing natural and stimulated cycles, with serum hormone measurements taken every 3 days; 2) 50 women undergoing ovarian stimulation, with serum and follicular fluid (FF) hormones assessed at five-time points during final follicle maturation; 3) 12 women undergoing fertility preservation, with hormone concentrations evaluated via small antral follicle FF. Results In the early follicular phase, TCs primarily synthesise 17-OH-P4 while GCs produce limited P4, maintaining the P4 /17-OH-P4 ratio below one. As follicles reached follicle selection around 10 mm in diameter, P4 synthesis in GCs became upregulated but was mainly accumulated in FF. During final maturation, the enhanced activity of the enzyme HSD3B2 in GCs boosted P4 production with the P4 /17-OH-P4 ratio increasing to more than one. The luteal phase showed similar 17-OH-P4 levels to that of the follicular phase, but P4 production increased yielding a P4/17-OH-P4 ratio significantly above one. Conclusions The P4 /17-OH-P4 ratio reflects GC-TC activity during the follicular phase and following luteinisation in the corpus luteum. Managing GC function is key for reducing P4 during ovarian stimulation, but the concerted action of FSH and LH on GCs during the second half of the follicular phase makes this complex.