Laboratory of Reproductive Biology, Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.
The Fertility Clinic, Herlev Hospital, Herlev, Denmark.
Reprod Biomed Online. 2024 Aug;49(2):103853. doi: 10.1016/j.rbmo.2024.103853. Epub 2024 Jan 30.
How is the production of progesterone (P) and 17-hydroxy-P (17-OH-P) regulated between theca cells and granulosa cells during the follicular phase, during ovulation and after transformation into a corpus luteum?
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.
In the early follicular phase, theca cells primarily synthesized 17-OH-P while granulosa cells produced limited P, maintaining the P:17-OH-P ratio <1. As follicles reached follicle selection at a diameter of approximately 10 mm, P synthesis in granulosa cells was up-regulated, but P was mainly accumulated in follicular fluid. During final maturation, enhanced activity of the enzyme HSD3B2 in granulosa cells enhanced P production, with the P:17-OH-P ratio increasing to >1. The concentration of 17-OH-P in the luteal phase was similar to that in the follicular phase, but P production increased in the luteal phase, yielding a P:17-OH-P ratio significantly >1.
The P:17-OH-P 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 P 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.
在卵泡期、排卵期间以及转化为黄体后，颗粒细胞和卵泡膜细胞如何调节孕酮（P）和 17-羟孕酮（17-OH-P）的产生？
共检查了三个队列：（i）31 名接受自然和刺激周期的女性，每 3 天测量一次血清激素；（ii）50 名接受卵巢刺激的女性，在最后卵泡成熟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女性，通过小窦卵泡的卵泡液评估激素浓度。
在卵泡早期，卵泡膜细胞主要合成 17-OH-P，而颗粒细胞产生有限的 P，保持 P:17-OH-P 比值<1。当卵泡直径达到约 10mm 时，颗粒细胞中的 P 合成被上调，但 P 主要积累在卵泡液中。在最后成熟过程中，颗粒细胞中 HSD3B2 酶的活性增强，促进了 P 的产生，P:17-OH-P 比值增加到>1。黄体期的 17-OH-P 浓度与卵泡期相似，但黄体期 P 的产生增加，P:17-OH-P 比值显著>1。
P:17-OH-P 比值反映了卵泡期和黄体期颗粒细胞和卵泡膜细胞的活性。在卵巢刺激过程中，管理颗粒细胞的功能是降低 P 浓度的关键，但 FSH 和 LH 在卵泡期后半期对颗粒细胞的协同作用使这一过程变得复杂。
