Ohara, A., Mori, T., Taii, S., Ban, C., & Narimoto, K. (1987). Functional differentiation in steroidogenesis of two types of luteal cells isolated from mature human corpora lutea of menstrual cycle. The Journal of clinical endocrinology and metabolism, 65(6), 1192-1200. https://doi.org/10.1210/jcem-65-6-1192
Ohara A, Mori T, Taii S, Ban C, Narimoto K. Functional differentiation in steroidogenesis of two types of luteal cells isolated from mature human corpora lutea of menstrual cycle. J Clin Endocrinol Metab. 1987;65(6):1192-1200. doi:10.1210/jcem-65-6-1192
Ohara, Akira, et al. "Functional differentiation in steroidogenesis of two types of luteal cells isolated from mature human corpora lutea of menstrual cycle." The Journal of clinical endocrinology and metabolism, vol. 65, no. 6, 1987, pp. 1192-1200.
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Enriched small and large cell fractions were prepared from mature corpora lutea from 15 women in the midluteal phase by enzymatic dissociation, followed by Percoll gradient centrifugation. The steroidogenic function of each cell type was assessed by measuring the gonadal steroids released into the incubation medium. The large cell fraction was estimated to be 97% pure, with minimal contamination by small cells, whereas the small cell fraction was approximately 68% pure, being contaminated with 10% large cells and 22% nonsteroidogenic cells. In the unstimulated state, large cells were approximately 2-fold more potent in progesterone formation and aromatase activity, but only half as potent in androstenedione and testosterone formation as an equal number of small cells. When stimulated with hCG, the small cells responded with significant increases in progesterone, androstenedione, and testosterone release, but the large cells did not. Both cell types secreted estrone and 17 beta-estradiol in the presence of androgen substrate, but the addition of FSH significantly stimulated aromatization only in large cells. Thus, small and large human luteal cells have steroidogenic properties similar to those exhibited by follicular thecal and granulosa cells, respectively.
The null hypothesis of this study is that the patterns of steroid secretion exhibited by the human corpus luteum in response to exogenous human chorionic gonadotropin stimulation are independent of corpus luteum age at the time of treatment. Twenty-five normally cycling women in whom the midcycle urinary luteinizing hormone surge (luteal day 0) was identified and from whom blood samples were obtained daily from cycle day 11 until menses were prospectively randomized to receive no treatment (group I, n = 5) or exogenous human chorionic gonadotropin 5000 IU administered intramuscularly on luteal day 0 (group II, n = 5), +4 (group III, n = 5), +8 (group IV, n = 5), or +12 (group V, n = 5). Serum concentrations of estrone, estradiol, progesterone, 17-hydroxyprogesterone, and androstenedione were measured by specific radioimmunoassays in all subjects; serum human chorionic gonadotropin concentrations were determined by immunoradiometric assay in treated subjects. Serum human chorionic gonadotropin levels (mean +/- SEM) were virtually identical among treatment groups (p greater than 0.05). Luteal phase duration (mean +/- SEM) was prolonged (p less than 0.05) only in group V (18.4 +/- 0.5 days) compared with untreated subjects (group I 13.8 +/- 0.7 days). In all groups estrone and 17-hydroxyprogesterone concentrations closely paralleled those of estradiol and progesterone, respectively. Steroid data and progesterone/estradiol ratios (mean +/- SEM) in groups I and II were indistinguishable and were combined (control, n = 10). Group III subjects exhibited patterns of steroid secretion similar to groups I and II, although progesterone was moderately increased after human chorionic gonadotropin treatment. In groups IV and V, progesterone increased (p less than 0.05) 1 day after human chorionic gonadotropin and remained elevated for 5 to 6 days; a 4-day rise (p less than 0.05) in estradiol began 3 days after treatment, and androstenedione rose modestly in parallel. Progesterone/estradiol ratios in groups III through V increased (p less than 0.05) approximately twofold after human chorionic gonadotropin treatment and remained elevated for 4 to 5 days. The human corpus luteum exhibits distinct age-dependent patterns of steroid secretion in response to exogenous human chorionic gonadotropin stimulation, an observation that may have clinical implications regarding the empirical use of exogenous human chorionic gonadotropin in support of luteal function.
Filicori M et al., 1984·J Clin Invest·Free full text on PubMed Central
The pattern of episodic gonadotropin release was studied in 15 normal female volunteers during the luteal phase of the menstrual cycle with 24 h of blood sampling for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels at 10-min intervals. Six subjects (two in the early, two in the mid-, and two in the late luteal phase) also had each of these specimens processed for progesterone levels. A progressive slowing of LH pulsations was present across the luteal phase with the mean LH pulse frequency declining from 15.2 pulses/24 h in the early to 8.4/24 h in the late luteal phase. A trend towards reduction in the amplitude of LH pulses was also observed (12.3 +/- 2.2 SD mIU/ml in the early vs. 8.6 +/- 3.4 mIU/ml in the late luteal phase; NS). In addition, LH pulses of heterogeneous amplitude were identified during the same 24-h study. The mean +/- SD of the larger and of the smaller LH pulses was 16.9 +/- 4.7 and 2.3 +/- 1.0 mIU/ml, respectively (P less than 0.001). While the slowing of the frequency of all LH pulses correlated well (r = 0.80, P less than 0.001) with the day of the luteal phase and poorly with the actual plasma progesterone levels, the incidence of the small LH pulses was highest in the mid-luteal phase and correlated well with the mean progesterone plasma levels (r = 0.63, P less than 0.01). In the early luteal phase, the pattern of progesterone secretion was stable over the 24-h studies and showed no relationship to episodic LH release. In contrast, in the midand late luteal phase, plasma progesterone concentrations rapidly fluctuated during the 24-h studies from levels as low as 2.3 to peaks of 40.1 ng/ml, often within the course of minutes. Progesterone increments closely attended episodes of LH release, as documented by the significant (P less than 0.05) cross-correlation between LH and progesterone levels, at time lags of 25-55 min. The results of this study indicate that in the human luteal phase: (a) the frequency of pulsatile release of LH declines progressively and correlates well with the duration of exposure to progressively and correlates well with the duration of exposure to progesterone; (b) the amplitude of LH pulses varies with the appearance of an increased percentage of smaller pulses correlating well with the acute level of progesterone; (c) in the early luteal phase, the pattern of progesterone secretion is stable; (d) in the midand late luteal phase, progesterone secretion is episodic, and correlates with LH pulsatile release; and (e) single progesterone estimations in the midand late luteal phase do not accurately reflect corpus luteum adequacy.
Women with luteal phase deficiency have been shown to have an increased frequency of luteinizing hormone pulses in the early follicular phase of the menstrual cycle. Because progesterone is known to modulate luteinizing hormone secretion, it has been hypothesized that the decreased progesterone secretion in a previous luteal phase deficiency cycle could lead to the abnormal luteinizing hormone secretory pattern in the ensuing early follicular phase. With the possibility that the higher luteinizing hormone pulse frequency might lead to another deficient luteal phase, it becomes conceivable that luteal phase deficiency could be self-perpetuating. To test this hypothesis, luteal phase deficiency was induced in six normal women by decreasing luteinizing hormone support of the corpus luteum with a gonadotropin-releasing hormone antagonist Nal-Glu, administered twice daily beginning in the midluteal phase after a control cycle. During the antagonist-treated luteal phase, each subject met the predetermined criteria for induced luteal phase deficiency: a 33% or greater decrease in integrated progesterone from the control cycle and an integrated progesterone level less than 100 ng/ml per day. Luteinizing hormone secretion patterns were determined by frequent blood sampling performed every 10 minutes for 12 hours in the early follicular phase of the control cycle and the cycle after antagonist administration. Daily luteal progesterone levels were measured in the control, treatment, and posttreatment cycles. Each volunteer served as her own control. Standard parameters were compared between the control and posttreatment pulse studies in the early follicular phase: (1) luteinizing hormone pulse frequency was 9.5 +/- 1.0 vs 10.0 +/- 0.9 pulses/12 hours, control vs posttreatment, respectively, p = 0.5; (2) luteinizing hormone pulse amplitude was 11.0 +/- 1.3 vs 12.0 +/- 2.2 ng/ml, p = 0.6; and (3) luteinizing hormone mean level was 19.4 +/- 2.3 vs 22.2 +/- 3.3 ng/ml, p = 0.1. Corpus luteum function was also compared between the control and posttreatment cycles. Luteal phase length was 13.7 +/- 0.6 vs 12.7 +/- 0.6 days, p = 0.08. Integrated progesterone values were 136.9 +/- 12.9 vs 130.5 +/- 11.3 ng/ml per day, p = 0.5. Therefore no discernible abnormalities in early follicular luteinizing hormone secretions or corpus luteum secretion of progesterone occurred after an induced luteal phase deficiency cycle.(ABSTRACT TRUNCATED AT 400 WORDS)
The pulsatile release pattern of LH during the entire menstrual cycle is well defined; however, the response of corpora lutea to these LH pulses in patients suffering from corpus luteum insufficiencies (CLI) is largely unknown. Patients suffering from CLI were selected from infertile patients on the basis of low progesterone (P < 25 nmol/L) in a blood sample withdrawn during a monitoring cycle. During the next cycle, nine blood samples were collected during the follicular and luteal phase and follicular development was assessed by vaginal sonography. Of 109 patients who had a CLI in the monitoring cycle, 55 had a CLI again, and 38 women agreed to undergo assessment of pulsatile hormone secretion. These women again had P < 25 nmol/L at days 6 and 7 of the luteal phase and blood samples were withdrawn through antecubital vein catheters from 0900-1700 h at 10-min intervals on days 7, 8, or 9 following ovulation. From 38 patients with such defined CLI, 16 (42%) had no LH episode and significantly lower basal LH levels in comparison with 14 control subjects. Thirteen (34%) of the patients had normal appearing LH episodes despite too low P and E2 concentrations, but their CL did not react to the LH episodes. The remaining 9 patients (24%) had normal LH episodes; their CL reacted to these episodes, but their basal P levels were too low. In all blood samples LH was not only determined using an immunoassay but also by the mouse Leydig cell testosterone production bioassay. It could be established that no CLI exists, which is due to the release of bioinactive LH. It is anticipated that the differentiation of three different types of CLI, one of hypothalamic and two of ovarian origin, may allow the development of differential diagnostic and therapeutic tools in the future.
Reproductive Endocrinology › Luteal Phase › Corpus Luteum Function · Menstrual Cycle › Cycle Physiology › Luteal Phase
PMID 3119652 3119652 DOI 10.1210/jcem-65-6-1192 10.1210/jcem-65-6-1192 Ohara et al. 1987, Ohara 1987
Cite this article
Ohara, A., Mori, T., Taii, S., Ban, C., & Narimoto, K. (1987). Functional differentiation in steroidogenesis of two types of luteal cells isolated from mature human corpora lutea of menstrual cycle. The Journal of clinical endocrinology and metabolism, 65(6), 1192-1200. https://doi.org/10.1210/jcem-65-6-1192
Ohara A, Mori T, Taii S, Ban C, Narimoto K. Functional differentiation in steroidogenesis of two types of luteal cells isolated from mature human corpora lutea of menstrual cycle. J Clin Endocrinol Metab. 1987;65(6):1192-1200. doi:10.1210/jcem-65-6-1192
Ohara, Akira, et al. "Functional differentiation in steroidogenesis of two types of luteal cells isolated from mature human corpora lutea of menstrual cycle." The Journal of clinical endocrinology and metabolism, vol. 65, no. 6, 1987, pp. 1192-1200.
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