Abstract：
OBJECTIVE: How is the production of progesterone (P4) and 17-hydroxy-P4 (17-OH-P4) regulated between theca cells and granulosa cells during the follicular phase, during ovulation and after transformation into a corpus luteum?
METHODS: Three cohorts were examined: (i) 31 women undergoing natural and stimulated cycles, with serum hormone measurements taken every 3 days; (ii) 50 women undergoing ovarian stimulation, with hormone concentrations in serum and follicular fluid assessed at five time points during final follicle maturation; and (iii) 12 women undergoing fertility preservation, with hormone concentrations evaluated via the follicular fluid of small antral follicles.
RESULTS: In the early follicular phase, theca cells primarily synthesized 17-OH-P4 while granulosa cells produced limited P4, maintaining the P4:17-OH-P4 ratio <1. As follicles reached follicle selection at a diameter of approximately 10 mm, P4 synthesis in granulosa cells was up-regulated, but P4 was mainly accumulated in follicular fluid. During final maturation, enhanced activity of the enzyme HSD3B2 in granulosa cells enhanced P4 production, with the P4:17-OH-P4 ratio increasing to >1. The concentration of 17-OH-P4 in the luteal phase was similar to that in the follicular phase, but P4 production increased in the luteal phase, yielding a P4:17-OH-P4 ratio significantly >1.
CONCLUSIONS: The P4:17-OH-P4 ratio reflects the activity of granulosa cells and theca cells during the follicular phase and following luteinization in the corpus luteum. Managing the function of granulosa cells is key for reducing the concentration of P4 during ovarian stimulation, but the concerted action of FSH and LH on granulosa cells during the second half of the follicular phase makes this complex.
METHODS: Three cohorts were examined: (i) 31 women undergoing natural and stimulated cycles, with serum hormone measurements taken every 3 days; (ii) 50 women undergoing ovarian stimulation, with hormone concentrations in serum and follicular fluid assessed at five time points during final follicle maturation; and (iii) 12 women undergoing fertility preservation, with hormone concentrations evaluated via the follicular fluid of small antral follicles.
RESULTS: In the early follicular phase, theca cells primarily synthesized 17-OH-P4 while granulosa cells produced limited P4, maintaining the P4:17-OH-P4 ratio <1. As follicles reached follicle selection at a diameter of approximately 10 mm, P4 synthesis in granulosa cells was up-regulated, but P4 was mainly accumulated in follicular fluid. During final maturation, enhanced activity of the enzyme HSD3B2 in granulosa cells enhanced P4 production, with the P4:17-OH-P4 ratio increasing to >1. The concentration of 17-OH-P4 in the luteal phase was similar to that in the follicular phase, but P4 production increased in the luteal phase, yielding a P4:17-OH-P4 ratio significantly >1.
CONCLUSIONS: The P4:17-OH-P4 ratio reflects the activity of granulosa cells and theca cells during the follicular phase and following luteinization in the corpus luteum. Managing the function of granulosa cells is key for reducing the concentration of P4 during ovarian stimulation, but the concerted action of FSH and LH on granulosa cells during the second half of the follicular phase makes this complex.
摘要：
目的：在卵泡期，孕酮（P4）和17-羟基-P4（17-OH-P4）的产生如何在卵泡膜细胞和颗粒细胞之间调节，在排卵过程中和转化为黄体后？
方法：检查了三个队列：（i）31名妇女经历自然和刺激周期，每3天进行血清激素测量；（ii）50名接受卵巢刺激的妇女，在最终卵泡成熟期间的五个时间点评估血清和卵泡液中的激素浓度；（iii）12名接受生育力保存的妇女，通过小窦卵泡的卵泡液评估激素浓度。
结果：在卵泡早期，卵泡膜细胞主要合成17-OH-P4,而颗粒细胞产生有限的P4,维持P4:17-OH-P4比率<1。当卵泡以大约10毫米的直径到达卵泡选择时，颗粒细胞中的P4合成上调，P4主要积累在卵泡液中。在最后的成熟过程中，颗粒细胞中HSD3B2酶的活性增强了P4的产生，P4:17-OH-P4比例增加到>1。黄体期17-OH-P4浓度与卵泡期相似,但P4产量在黄体期增加，产生P4:17-OH-P4比率显著>1。
结论：P4:17-OH-P4比值反映了卵泡期和黄体发育后颗粒细胞和卵泡膜细胞的活性。管理颗粒细胞的功能是降低卵巢刺激过程中P4浓度的关键，但是在卵泡期的后半期，FSH和LH对颗粒细胞的协同作用使这种情况变得复杂。
方法：检查了三个队列：（i）31名妇女经历自然和刺激周期，每3天进行血清激素测量；（ii）50名接受卵巢刺激的妇女，在最终卵泡成熟期间的五个时间点评估血清和卵泡液中的激素浓度；（iii）12名接受生育力保存的妇女，通过小窦卵泡的卵泡液评估激素浓度。
结果：在卵泡早期，卵泡膜细胞主要合成17-OH-P4,而颗粒细胞产生有限的P4,维持P4:17-OH-P4比率<1。当卵泡以大约10毫米的直径到达卵泡选择时，颗粒细胞中的P4合成上调，P4主要积累在卵泡液中。在最后的成熟过程中，颗粒细胞中HSD3B2酶的活性增强了P4的产生，P4:17-OH-P4比例增加到>1。黄体期17-OH-P4浓度与卵泡期相似,但P4产量在黄体期增加，产生P4:17-OH-P4比率显著>1。
结论：P4:17-OH-P4比值反映了卵泡期和黄体发育后颗粒细胞和卵泡膜细胞的活性。管理颗粒细胞的功能是降低卵巢刺激过程中P4浓度的关键，但是在卵泡期的后半期，FSH和LH对颗粒细胞的协同作用使这种情况变得复杂。
