Circuits involved in controlling the LH surge and sexual behaviors were thought to be influenced by estradiol and progesterone synthesized in the ovary and perhaps the adrenal.
The secretory rates of progesterone and 20α-hydroxypregn-4-en-3-one (20α-OHP) from the ovary and the concentration of both progestins in the ovarian tissues were determined during the estrous cycle in 4-day cyclic rats illuminated 12 hrs. a day (8a.m. to 8 p.m.). The progesterone secretion increased twice a cycle, markedly on the evening (peak at 7p.m.) of the day of proestrus and slightly on the afternoon of the day of early diestrus. The prompt and tremendous increase of progesterone secretion at the preovulatory stage almost synchronized with the release of luteinizing hormone (LH). It was also demonstrated that a marked preovulatory rise of progesterone secretion depended upon pituitary LH discharge, and a slight increase in both progestin secretions-at early diestrus was not dependent on the pituitary function at that stage. These facts together with the following fmdings, (a) an enormous increase in the ratio of progesterone over total progestin (progesterone plus 20α-OH-P) in the ovarian venous blood at the preovulatory stage, (b) the secretory pattern of 20α-OH-P which roughly paralleled with that of progesterone at the diestrous phase, and (c) a higher concentration of progesterone in the ovary as compared with that of 20α-OH-P at the diestrous phase and its reverse relationship of the concentrations at the stages of proestrus and estrus, suggest that a drastic shift occurs at the sites of progesterone synthesis from the involuting corpora lutea to the LH sensitive ripening follicles or interstitial tissues under the influence of released LH which exerts both luteinizing effect and steroidogenic action on the ovary, and the present data suggest that the newly developed corpora lutea after ovulation gain the automaticity of progestin synthesis, storage and secretion independently of the pituitary function.
Our results demonstrate for the first time that fractalkine and CX3CR1 are expressed in human ovarian tissues and human luteinising granulosa cells. Higher expression of fractalkine was found in luteinising granulosa cells than in granulosa cells in the follicular phase. Fractalkine can augment biosynthesis of progesterone in a dose-dependent manner but without affecting estradiol production by enhancing key steroidogenic enzymes in transcript levels. Increased expression of fractalkine/CX3CR1 can enhance progesterone production in luteinised human granulosa cells, which is consistent with the results of previous studies on rats . To our knowledge, this is the first detailed report of fractalkine and CX3CR1 expression and the first description of their functions in human ovary and granulosa cells.
In our study, progesterone secretion was stimulated dose dependently by hCG in cultured luteinised granulosa cells. Previous studies have shown that IL-1B, prolactin and pituitary adenylate cyclase-activating polypeptide were found to be increased by the preovulatory LH/hCG surge and could promote progesterone biosynthesis and luteinisation [-]. In this study, progesterone production was further increased when cells were co-treated with fractalkine and hCG. Fractalkine significantly stimulated progesterone production in a dose-dependent manner. Higher expression of fractalkine was found in luteinised granulosa cells than in granulosa cells in the follicular phase. Above results indicated that fractalkine plays important roles in the ovary luteinising process as autocrine/paracrine factors. The finding that fractalkine could increase hCG-stimulated progesterone production may have clinical relevance in some reproductive endocrine diseases, such as corpus luteum function defect and polycystic ovary syndrome with insufficient progesterone, which results in menstrual disorder and abortion. Further study may lay the foundation for clinical treatment of these diseases.
Fractalkine and CX3CR1 were found to express in human ovary and luteinising granulosa cells. Fractalkine can increase the biosynthesis of progesterone in a dose-dependent manner by enhancing transcript levels of key steroidogenic enzymes.
Single cells were prepared from the luteinized rat ovary, and the characteristics of progesterone synthesisby these cells were examined. The isolated luteal cells were viable and functional, and respond toluteinizing hormone (LH) stimulation by synthesizing progesterone in vitro. In the absence of exogenousglucose, the rate of progesterone synthesis was 0.23 ng/ml/min. LH increased this rate 2-fold, and the durationof the initial linear phase of this reaction was sustained for up to 60 min, compared to the controlswhich were linear for only 15 min. This effect was dose-related: maximal stimulation was achieved with1 J1g LH/ml, while a minimal but significant stimulation was elicited with 61 pg/ml. This steroidogenicactivity was also increased by the addition of exogenous glucose and bovine serum albumin. These dataserve to establish the optimum conditions for the use of single cells in studies pertaining to mechanismof LH action.
Fractalkine and CX3CR1 were expressed in the human ovary and in luteinising granulosa cells. However, fractalkine expression was stronger in luteinising granulosa cells. Treatment with fractalkine augmented hCG stimulation of progesterone production in a dose-dependent manner with concomitant increases in transcript levels for key steroidogenic enzymes (StAR, 3-βHSD and CYP11A) but had no effect on estradiol biosynthesis(P