Serum Concentrations Of 17-hydroxyprogesterone Research Articles

Serum concentrations of 17-hydroxyprogesterone and dehydroepiandrosterone sulfate in women with polycystic ovary syndrome and their relation to the parameters of glucose metabolism

Serum concentrations of 17-hydroxyprogesterone and dehydroepiandrosterone sulfate in women with polycystic ovary syndrome and their relation to the parameters of glucose metabolism

Clinical characteristics of 21 infertile women with non-classic 21-hydroxylase deficiency

Objective: To investigate the clinical features of infertile women with non-classic 21-hydroxylase deficiency (21-OHD). Methods: The study enrolled 21 infertile women with non-classic 21-OHD in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2009 to December 2018. The clinical presentation, endocrine hormone, glucolipid metabolism and treatment outcome were retrospectively analyzed. The diagnosis of non-classic 21-OHD was comprehensively based on clinical and hormonal characteristics. Results: Among 21 cases, the age was (29.9±2.9) years, the mean age at menarche was (13.6±2.0) years, body mass index was (22.1±2.9) kg/m2, and 38% (8/21) had oligomenorrhea. Hirsutism was diagnosed in 3 cases (14%, 3/21). Clitoromegaly was seen in 14% (3/21) and polycystic ovarian morphology was found in 33% (7/21) of the patients. The mean serum level of basal progesterone was (11.3±21.0) nmol/L, with 48% (10/21) having high basal progesterone level; after therapy by glucocorticoid, the level of progesterone was (1.9±2.0) nmol/L. Serum 17-hydroxyprogesterone concentration was (66.4±123.6) nmol/L; after therapy by glucocorticoid, it was (2.4±1.8) nmol/L. In the study increased testosterone, androstenedione and dehydroepiandrosterone sulfate were present in 62% (13/21), 52% (11/21) and 43% (9/21), respectively; and 52% (11/21) of patients manifested androgen excess and basal progesterone elevation; androgen levels decreased after therapy by glucocorticoid. The pregnancy rate was 76% (16/21). Out of 19 pregnancies, 6/19 ended in spontaneous miscarriages. Conclusions: Infertile women with non-classic 21-OHD are characterized by hyperandrogenism and basal progesterone elevation, whereas gonad axis disorder is not apparent. After no response to conventional therapy, adult infertile women with non-classic 21-OHD could achieve a desirable pregnancy outcome with proper treatment of glucocorticoid.

Assessment of the body composition of patients with polycystic ovary syndrome using dual-energy X-ray absorptiometry.

To compare the body composition among patients with polycystic ovary syndrome (PCOS) and patients without PCOS. A cross-sectional study enrolled patients aged 12-39years, with body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) at least 18.5 but below 25, who attended the Endocrine Gynecology Clinic of Santa Casa de Sao Paulo School of Medical Sciences, Brazil, between January 1, 2014, and July 31, 2015. Anthropometric measurements, metabolic and androgenic profiles, and dual-energy X-ray absorptiometry measurements were compared between patients with PCOS and those without PCOS. In total, 102 eligible patients attended the study clinical during the study period; 43 were excluded owing to not meeting the inclusion criteria or declining to undergo complete study testing, and 15 withdrew from the study. Of the 44 participants, 28 had PCOS and 16 were included in the control group. Serum 17-hydroxyprogesterone concentration (P=0.046), leg-fat (P=0.031), and truncal-fat (P=0.001) were all higher among patients with PCOS. The present study demonstrated increased truncal and leg fat among women with PCOS. The study did not detect any difference in insulin parameters but larger studies could be more suitably powered to investigate this. CLINICALTRIALS.GOV: NCT02467751.

Cortisol measurement in patients receiving metyrapone therapy

Current guidance recommends titrating the dose of metyrapone against serum cortisol concentration, in patients under medical management of Cushing's syndrome. In the UK, this almost always involves measuring serum cortisol concentration by immunoassay, the performance of which is questionable in the presence of altered steroid metabolism. Sera from two patients receiving metyrapone were analysed using a liquid chromatography tandem mass spectrometry (MS) steroid assay to identify which steroids, if any, were elevated in these patients. In addition, control serum was spiked with a series of steroids to identify any potential positive interferences in a cortisol immunoassay. Serum 11-deoxycortisol concentration was elevated in both of the patients studied. One patient also had an elevated serum 17-hydroxyprogesterone concentration and the other an elevated androstenedione. In addition, the results of the interference studies indicated that the cortisol immunoassay was susceptible to interference from 11-deoxycortisol, 17-hydroxyprogesterone and 21-deoxycortisol. However, the magnitude of interference, in the serum cortisol immunoassay, due to these three steroids could not account for the discrepancy between the cortisol concentrations measured by immunoassay and those measured by MS. Both clinicians and laboratory staff should be aware of these interferences when monitoring patients undergoing treatment with metyrapone, and consequently serum should be measured in these patients by MS, not by immunoassay.

Management of Altered Hydrocortisone Pharmacokinetics in a Boy with Congenital Adrenal Hyperplasia Using a Continuous Subcutaneous Hydrocortisone Infusion

Conventional hydrocortisone dosing schedules do not mimic the normal circadian rhythm of cortisol, making it difficult to optimize treatment in congenital adrenal hyperplasia (CAH). We report a 14.5-year-old boy with CAH who had reduced bioavailability [42% (normal 80% orally and 100% by im route)] and increased clearance [half-life 50 min (normal range, 70-100 min)] of oral doses of hydrocortisone leading to ambient serum 17-hydroxyprogesterone concentrations of 400 nmol/liter (14.5 ng/ml) and androstenedione concentrations of 24.9 nmol/liter (7.1 ng/ml). Using a continuous but variable sc hydrocortisone infusion via an insulin pump, rapid control of his CAH was attained with a normal cortisol circadian profile. Average daily hydrocortisone dose was 17.4-18.6 mg/m(2), which produces on average 24-h serum cortisol and 17-hydroxyprogesterone concentrations of 316 nmol/liter (115 ng/ml) and 4.3 nmol/liter (1.4 ng/ml), respectively. Therapy has been maintained over 4 yr with suppression of normal adrenal androgen production and normal progression through puberty. Continuous sc infusion of hydrocortisone may prove a valuable adjunct to therapy for CAH, particularly in patients requiring high doses of oral hydrocortisone and in those with abnormal hydrocortisone pharmacokinetics.

Assessment of cytologic evaluation of preputial epithelial cells as a diagnostic test for detection of adrenocortical disease in castrated ferrets

To determine whether results of cytologic evaluation of preputial epithelial cells correspond to results of a serum endocrine hormone assay and clinical signs associated with adrenocortical disease in castrated ferrets. 13 clinically normal ferrets and 8 ferrets with signs of adrenocortical disease. Blood and preputial lavage samples were collected from each ferret. Serum samples were submitted to the University of Tennessee Veterinary Diagnostic Laboratory for performance of an endocrine hormone assay. Differential epithelial cell counts were performed on preputial lavage samples to determine the percentage of cornified cells. Results of cytologic evaluation were compared with results of the endocrine hormone assay and clinical status of ferrets. The percentage of cornified preputial epithelial cells was not significantly correlated with serum 17B-estradiol or androstenedione concentration but was significantly correlated with serum 17-hydroxyprogesterone concentration (r = 0.60). The percentage of cornified preputial epithelial cells was higher in ferrets with clinical signs of adrenocortical disease (mean +/- SD, 71.3 +/- 16.9%) than in clinically normal ferrets (55.5 +/- 19.0%). Cornification of preputial epithelial cells was correlated with an increase in serum 17-hydroxyprogesterone concentration as well as clinical signs of adrenocortical disease in castrated ferrets. Additional investigation is needed to elucidate the mechanism of preputial epithelial cell cornification in castrated ferrets.

Evaluation of serum 17-hydroxyprogesterone concentration after administration of ACTH in dogs with hyperadrenocorticism

To evaluate serum 17-hydroxyprogesterone (17-OHP) concentration measurement after administration of ACTH for use in the diagnosis of hyperadrenocorticism in dogs. Prospective study. 110 dogs. Serum 17-OHP concentrations were measured before and after ACTH stimulation in 53 healthy dogs to establish reference values for this study. Affected dogs had pituitary-dependent (n = 40) or adrenal tumor-associated (12) hyperadrenocorticism or potentially had atypical hyperadrenocorticism (5; diagnosis confirmed in 1 dog). In affected dogs, frequency interval and borderline and abnormal serum 17-OHP concentrations after ACTH stimulation were determined. Serum cortisol concentrations were assessed via low-dose dexamethasone suppression and ACTH stimulation tests. In healthy dogs, serum 17-OHP concentration frequency intervals were grouped by sex and reproductive status (defined as < 95th percentile). Frequency intervals of serum 17-OHP concentrations after ACTH stimulation were < 77, < 2.0, < 3.2, and < 3.4 ng/mL (< 23.3, < 6.1, < 9.7, and < 10.3 nmol/L) for sexually intact and neutered females and sexually intact and neutered males, respectively. In 53 dogs with confirmed hyperadrenocorticism, serum cortisol concentrations after ACTH stimulation and 8 hours after administration of dexamethasone and serum 17-OHP concentrations after ACTH stimulation were considered borderline or abnormal in 79%, 93%, and 69% of dogs, respectively. Two of 5 dogs considered to have atypical hyperadrenocorticism had abnormal serum 17-OHP concentrations after ACTH stimulation. Serum 17-OHP concentration measurement after ACTH stimulation may be useful in the diagnosis of hyperadrenocorticism in dogs when other test results are equivocal.

A preponderance of basic luteinizing hormone (LH) isoforms accompanies inappropriate hypersecretion of both basal and pulsatile LH in adolescents with polycystic ovarian syndrome.

We recently demonstrated that adolescent girls with polycystic ovarian syndrome (PCOS) exhibit augmented LH secretion due to an increase in immunofluorometric and deconvolution-estimated LH secretory burst mass and pulse frequency. Concurrently, we inferred either a prolongation of apparent (endogenous) LH half-life or elevated basal (nonpulsatile) LH release in PCOS. The in vivo half-life of LH molecules can be affected by the oligosaccharide side-chains, which also modify in vitro bioactivity and electrostatic change. Accordingly, as a surrogate estimator of altered endogenous LH half-life and/or biopotency in PCOS, we characterized the isoelectric properties of secreted LH isoforms and determined their in vitro biological activity in adolescent girls with PCOS compared with healthy age-matched eumenorrheic controls. To this end, 12-h (overnight) serum samples from PCOS patients (n = 12) and normal adolescents (n = 10) were pooled by subject. Bioactive LH concentrations were then quantitated in a rat Leydig cell in vitro bioassay, and immunological activity was determined by immunofluorometry. The distribution of LH isoforms was evaluated by preparative chromatofocusing (pH window, 10.5 to <4.0) of samples further combined to yield three independent serum pools for each of the patient and control groups. Fasting serum concentrations of 17-hydroxyprogesterone (17-OHP), androstenedione, testosterone, estrone, estradiol, and sex hormone-binding globulin were determined as possible endocrine correlates of LH isotypes. Mean serum concentrations of immunoreactive and bioactive LH in adolescents with PCOS were 3 and 2 times higher than values in controls: immunoreactive: PCOS, 7.8+/-0.9; controls: 2.6+/-0.3 IU/L (P < 0.001); and bioactive: PCOS, 52+/-10; controls, 25+/-4.1 IU/L (P = 0.002), respectively. Bioactive LH concentrations correlated positively with 17-OHP (P = 0.022), androstenedione (P = 0.012), and testosterone (P = 0.046) concentrations in PCOS. Chromatofocusing of LH isoforms disclosed greater LH immunoreactivity at pI values greater than 8 and 7.99-7.0 in adolescents with PCOS compared with controls (P = 0.031). The percentage of basic LH isoforms was related positively to serum concentrations of 17-OHP (P = 0.032), androstenedione (P = 0.046), and testosterone (P = 0.040). In conclusion, the present isotype analysis demonstrates elevated in vitro LH bioactivity and a preponderance of basic LH isoforms in girls with PCOS. Since previously reported heterologous in vivo assays of LH kinetics point toward accelerated removal of such alkaline isotypes, our findings would favor the earlier alternative hypothesis of inappropriate hypersecretion of basal (interpulse) LH rather than prolongation of the LH half-life as the mechanism for elevated interpulse serum LH concentrations in adolescents with PCOS. In ensemble, the foregoing data thus suggest 3-fold amplification of basal LH secretion as well as both a heightened amplitude and frequency of the pulsatile mode of LH release in PCOS.

Effect of gender, birth weight and gestational age on serum 17-hydroxyprogesterone concentration and distribution among neonates in Saudi Arabia.

Blood samples from 813 newborns were spotted on to filter paper and the 17-hydroxyprogesterone concentration was measured using the Delfia (R) fluorometric immunoassay. The median, mean, and standard deviation (SD) for the total population were 20, 21 and (11) nmol/L respectively. Males had significantly higher levels than females with median, mean and (SD) of 22, 22 and (12) nmol/L. Similarly, low birth weight babies were found to have significantly higher levels than normal birth weight babies with median, mean and (SD) of 21, 24 (12) nmol/L. Preterm babies were also found to have significantly higher levels than full term babies, with median, mean and (SD) of 25, 29 (16) nmol/L. As experienced elsewhere, those factors should be taken into consideration when considering a cut-off point in any neonatal screening program for congenital adrenal hyperplasia.

Adrenal incidentaloma and patients with homozygous or heterozygous congenital adrenal hyperplasia.

Adrenal tumors are being detected more frequently in consequence of the wider application of increasingly sensitive radiological investigation techniques. According to the working hypothesis that more silent adenomas could develop from hyperplastic tissue areas under increased stimulation of the adrenal cortex, heterozygous and homozygous patients with congenital adrenal hyperplasia (CAH) were studied. A high incidence of adrenal masses, nearly 82% in homozygous and 45% in heterozygous patients, was found. There was no correlation between tumor size and serum 17-hydroxyprogesterone concentrations. These tumors are, therefore, probably silent adenomas. On the basis of these results, CAH should always be ruled out in the case of incidentally detected adrenal masses. Since CAH is a relatively frequent disease, and the adrenal carcinoma belongs to the rarest malignant tumors, a malignant transformation of these tumors seems to be unlikely.

Androgen receptor disorder in three brothers with bifid prepenile scrotum and hypospadias

Three brothers with congenital transposition of the penis, scrotal hypospadias, bifid scrotum, and bilateral undescended testes are described. Further signs of incomplete virilization, but no gynecomastia were seen. LH and FSH were elevated, whereas testosterone levels were reduced or in the normal range. Serum concentrations of 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, 5 alpha-dihydrotestosterone and estradiol measured in two affected brothers were in the normal range. Fibroblasts from scrotal skin biopsies performed in two patients showed normal 5 alpha-reductase activity (419 and 214 pmol.(mg protein)-1.h-1; normal greater than 1), whereas androgen receptors had reduced maximal binding capacity (Bmax 4 and 14 fmol.(mg protein)-1; normal greater than 18) and an increased equilibrium dissociation constant (0.7 and 1.26 nmol/l: normal 0.2 +/- 0.08) indicating a quantitative and qualitative androgen receptor defect. These patients represent a further variant of androgen insensitivity.

Molecular Characterization of a Leydig Cell Tumor Presenting as Congenital Adrenal Hyperplasia*

We present an unusual patient with a Leydig cell tumor to show that greatly elevated serum concentrations of 17-hydroxyprogesterone (17OHP) may not be diagnostic of congenital adrenal hyperplasia (CAH). A 3.5-yr-old boy had a small testicular mass and plasma 17OHP concentrations of 147-333 nmol/L (4,850-11,000 ng/dL), suggesting CAH with adrenal rests. However, normal plasma cortisol values and the unresponsiveness of the 17OHP concentration to dexamethasone suppression or ACTH stimulation suggested a diagnosis of Leydig cell tumor. A 4-fold elevation in plasma 21-deoxycortisol compared with a 200-fold elevation in 17OHP suggested that the elevated 17OHP derived from the normal pathway of testosterone synthesis in the testis. This was proven by normalization of all hormonal values after tumor resection. Compared to the abundance of mRNA for P450c17, the tumor contained unusually large amounts of mRNA for P450scc, the cholesterol side-chain cleavage enzyme, which is the rate-limiting step in steroid hormone synthesis. Increased P450scc activity, which increased the conversion of cholesterol to pregnenolone, apparently permitted the 17,20-lyase activity of P450c17 to become rate limiting, thus accounting for the increased secretion of 17OHP. Thus, Leydig cell tumors can produce quantities of 17OHP previously reported only in CAH due to 21-hydroxylase deficiency. The molecular characterization of steroidogenic mRNAs in this tumor indicates an unusual ratio in the expression of the genes for the steroidogenic enzymes, probably accounting for the unusual pattern of serum steroids.

Effect of short-term bile duct ligation on peripheral blood steroids urinary PGE 2 and the rate of sodium excretion in male rabbits

1. 1. Short-term bile duct ligation in male rabbits resulted in a significant reduction in the rate of sodium excretion after saline challenge (10 ml/kg/hr for 4 hr, P < 0.03). 2. 2. The reduction in the sodium excretory rate (14.3 ± 7.8 to 6.3 ± 5 μ-equiv/min, P < 0.03) was associated with an increased urinary PGE 2 excretion (200.9 ± 174 to 731.8 ± 1039.8 pg/min, P < 0.01) without significant change in serum aldosterone and cortisol concentrations. 3. 3. Serum progesterone concentration increased (37.2 ± 15.6 to 119.2 ± 34.6 ng/dl, P < 0.01) whereas serum 17-hydroxyprogesterone concentration declined after bile duct ligation suggesting the development of a 17-hydroxylase enzymatic block.

Urinary and serum steroid concentrations in the management of congenital adrenal hyperplasia. Lack of physiologic correlations.

Serum concentrations of 17-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, progesterone, testosterone, and androstenedione and 24-hour excretion of 17-ketosteroids and pregnanetriol were measured serially in 18 children with congenital adrenal hyperplasia (21-hydroxylase deficiency) during a two-year period. Correlations were sought between results of measurements of these steroids and clinical progress assessed by physical examination and skeletal maturity to determine if measurement of concentration of these substances at a single point in time could be used to gauge the dose of corticosteroids for optimum treatment. We found that these measurements of steroids were generally not useful indicators of optimum control of the disease. Repeated careful clinical examination and assessment of changes in growth velocity and skeletal maturation seem to be the best criteria on which to base dosage of corticosteroids used for therapy.

Luteal Function in Baboons with Administration of the Antiestrogen Ethamoxytriphetol (MER-25) Throughout the Luteal Phase of the Menstrual Cycle1

Administration of the antiestrogen ethamoxytriphetol (MER-25) during late baboon gestation has been reported to result in a marked decline in progesterone (P) production rate. Since both the placenta and corpus luteum appear to secrete P during late baboon gestation, this decline in P may reflect a loss in luteal and/or placental function. Therefore, the present study determined the effect of administration of the antiestrogen MER-25 upon serum steroid concentrations during the luteal phase of the baboon menstrual cycle, a tijne when the source of P is almost exclusively the corpus luteum, Six baboons were bled throughout a control menstrual cycle and during daily administration (15 mg/kg BW, p.o.) of MER25 throughout the luteal phase of the following cycle. Mean (± SEM) length of the luteal phase of the menstrual cycle was the same in baboons with no treatment (18 ± 0 days) and after MER-25 administration (18 ± 0 days). Mean (± SEM) serum concentrations of P were similar in the luteal phase with no treatment (5.2 ± 0.7 ng/ml) and during MER-25 administration (5.0 ± 0.6 ng/ml). Serum P attained similar peak values of concentration in the luteal phase before and after antiestrogen administration and was detectable in the serum for a similar duration of the lutes] phase of both cycles. Mean (± SEM) serum concentrations of 17-hydroxyprogesterone (17-01(P), which may also provide an index of lutes] function, were similar in the luteal phase of the menstrual cycle in baboons with no treatment (0.53 ± 0.20 nglml) and during administration of MER-25 (0.42 ± 0.15 ng/inl). Serum estradiol (E2) concentrations attained a peak at midcycle, then declined to low values, and MER-25 had no effect upon serum E2.

Serum Steroids and Pituitary Hormones in Infants with Particular Reference to Testicular Activity

We have determined the concentrations of pregnenolone, progesterone, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, testosterone, 5α-dihydrotestosterone, and androsterone in serum collected from 34 boys and 11 girls between 5–40 weeks of age, and we have compared these data with the concentrations of FSH, LH, and PRL in the same samples. Clear sex differences in the serum concentrations of testosterone and 5α-dihydrotestosterone were found to exist between 5–25 weeks of age, and during this period the serum concentrations of these steroids in the male infant population are similar to those in the lower normal adult male range. This sex difference is indicative of a high level of testicular steroidogenesis, which was also supported by the higher serum concentrations of 17- hydroxyprogesterone in boys compared to girls, between 10-25 weeks of age, and the good correlation between serum concentrations of 17-hydroxyprogesterone and testosterone in these boys. High serum concentrations of 5a-...

CONGENITAL ADRENAL HYPERPLASIA: SIMULTANEOUS DETERMINATION OF PLASMA ALDOSTERONE AND 17-HYDROXYPROGESTERONE

ABSTRACT Plasma levels of aldosterne and 17-hydroxyprogesterone were determined in 5 just diagnosed cases of congenital adrenal hyperplasia due to 21-hydroxylase deficiency without salt-loss before onset of therapy, and in 14 children suffering from the same disorder, under glucocorticoid therapy before and after withdrawal of therapy for one week as well as before and after ACTH-stimulation. Furthermore, urinary pregnanetriol, pregnanetriolone, 17-ketosteroids and 17-ketogenic steroids were determined with and without therapy. Serum concentrations of 17-hydroxyprogesterone in patients before onset of therapy were at least 40 times above the normal range (normal range: 0.39 ± 0.23 ng/ml determined in 19 children of age 1–12 years), aldosterone was also elevated (range 16.5–84.4 ng/100 ml, normal aldosterone being 7.3 ± 4.7 ng/ml). In contrast, well controlled patients (judged on urinary pregnanetriol-excretion) had normal aldosterone (one exception) and 17-hydroxyprogesterone levels below 5 ng/ml. Both steroids were well stimulated by ACTH. In 3 poorly controlled cases elevated pregnanetriol and 17-hydroxyprogesterone values up to 130.9 ng/ml were found. Withdrawal of therapy resulted in pronounced rise of aldosterone and 17-hydroxyprogesterone. Exogenous ACTH had no detectable effect in 7 cases leading to further stimulation in the other children. We found an excellent correlation between plasma 17-hydroxyprogesterone and urinary pregnanetriol (r = 0.84, P &lt; 0.003, n = 14). Fairly good correlation also exists between aldosterone and 17-hydroxyprogesterone values (r = 0.65, P &lt; 0.01, n = 14) in patients before the onset and after withdrawal of therapy. The data confirm the value of 17-hydroxyprogesterone determinations for diagnosis and management of congenital adrenal hyperplasia on the one hand, and the compensatory elevated aldosterone production in the non-salt-losing form of the disorder on the other.

The effect of prostaglandin F2 ? on endocrine parameters in early pregnancy

The luteolytic effect of prostaglandin f2alpha (PGF2alpha) has been well documented in a variety of primates. This property has not been proven in early human pregnancy. A study of the luteolytic activity of extraamnial administration of 5 mg PGF2alpha was carried out on 7 healthy women who were less than 6 weeks pregnant and on 4 women who were more than 9 weeks pregnant. Serum levels of 17beta-estradiol, 17-hydroxyprogesterone, progesterone and human chorionic gonadotropin (HCG) were measured by radioimmunoassay before, during and after the administration of PGF2alpha. Abortion was successfully induced in all the patients with early pregnancies, but in the control group of more mature pregnancies only one of the four women aborted. In the older pregnancies, the administration of 5 mg PGF2alpha caused no significant alteration in the serum levels of the measured hormones. In the younger pregnancies the serum concentration of 17beta-estradiol and progesterone decreased within hours after PGF2alpha administration. Serum 17-hydroxyprogesterone concentrations remained unchanged at a high level and declined significantly later in a manner similar to HCG. This discrepancy in the decline of 17-hydroxyprogesterone as opposed to progesterone and 17beta-estradiol may be explained by two mechanisms, the one mechanical, and the other secondary luteolytic. The marked increase of intrauterine pressure occurring within minutes after PGF2alpha instillation damages the fetoplacental unit. This leads to a decrease in the placental steroido-genesis and HCG production necessary for the maintenance of the corpus luteum.