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Differentiation of rat ovarian thecal cells: evidence for functional luteinization.

To determine if thecal cells of rat preovulatory (PO) follicles become functionally luteinized, theca from small antral (SA) and PO follicles were isolated before and 8 h after iv injection of an ovulatory dose (10 IU) of hCG. Thecal explants were cultured for 30 days in Dulbecco's Modified Eagle's Medium-Ham's F-12 medium containing 1% fetal calf serum (FCS) with or without 5 ng/ml ovine LH or 10 microM forskolin. Whereas theca from SA, hCG-treated SA, and PO follicles were dependent on LH or forskolin to maintain progesterone (greater than 10 ng/ml) and androstenedione (greater than 10 ng/ml) accumulation, luteinizing theca (hCG-treated PO) accumulated more than 10 ng/ml progesterone and more than 2 ng/ml androstenedione with or without LH or forskolin for 30 days. Granulosa cells were isolated from these same follicles and cultured under similar conditions, including 10 ng/ml testosterone and 25 ng/ml ovine FSH. Only granulosa cells isolated from luteinizing follicles (hCG-treated PO) maintained progesterone (greater than 20 ng/ml) and estradiol (10 ng/ml) accumulation with or without FSH or forskolin for 30 days. Basal concentrations of cAMP were 5 to 10-fold higher in thecal and granulosa cells from luteinizing follicles than in these tissues isolated from SA or PO follicles. We conclude that thecal cells as well as granulosa cells of rat PO follicles respond to the LH/hCG surge by becoming functionally luteinized, less dependent on LH, and capable of maintaining an increased accumulation of basal cAMP. Furthermore, the data suggest that one luteinizing thecal explant produces a similar amount of progesterone as one follicle equivalent of luteinizing granulosa cells. Thus, luteinized theca have the potential of contributing significantly to progesterone secretion by the mature rat corpus luteum.

Androstenedione↗

Characterization of the disposition of lutein after i.v. administration to rats.

Lutein is a carotenoid that has antioxidant effects. Although lutein has received much attention recently due to its antioxidant activities, little information about the pharmacokinetic properties of lutein is available. The disposition of lutein after i.v. administration has not been investigated because lutein is now used as a supplement. The present study was undertaken to acquire additional data on the disposition of lutein after i.v. administration. After i.v. administration, lutein is preferentially distributed to the liver, spleen and lung. Intravenous administration of lutein may provide effective antioxidant activities in these tissues, not only the eye. The results of this study should provide valuable data for drug development.

Animals↗

[Autoantibody to luteinizing hormone in patient with systemic lupus erythematosus (author's transl)].

One hundred microgram of luteinizing hormone releasing hormone was intravenously injected into 19 female patients with systemic lupus erythematosus and plasma luteinizing hormone levels before and after the injection were determined with a method of solid phase radioimmunoassay. In 4 patients among them, the basal levels of luteinizing hormone were abnormaly high. A question about the existence of autoantibodies to luteinizing hormone in the patient's plasma raised to explain the reason for the high level of luteinizing hormone. The results from 3 experiments for solution of this question were as follows. 1) The patient's plasma was proved to have a binding activity with labeled luteinizing hormone. 2) This binding activity is specifically inhibited by purified luteinizing hormone. 3) This binding activity was located in gamma-globulin fraction. From the results, the existence of autoantibodies to luteinizing hormone in the 2 patients' plasma was concluded.

Adolescent↗

Frequency of the allelic variant (Trp8Arg/Ile15Thr) of the luteinizing hormone gene in a Brazilian cohort of healthy subjects and in patients with hypogonadotropic hypogonadism.

PURPOSE: To evaluate the frequency of allelic variant Trp8Arg/Ile15Thr in the luteinizing hormone beta-subunit gene in a Brazilian population of healthy subjects and in patients with hypogonadotropic hypogonadism. SUBJECTS AND METHODS: Two hundred and two adults (115 women) with normal sexual function and 48 patients (24 women) with hypogonadotropic hypogonadism underwent a molecular study of the the luteinizing hormone beta-subunit gene using a polymerase chain reaction technique followed by enzymatic digestion with the restriction enzymes Nco I (for detection of the Trp8Arg point mutation) and Fok I (for detection of the Ile15Thr point mutation). Basal luteinizing hormone and FSH, testosterone, or estradiol levels were measured in 37 healthy subjects (21 women) and in 27 hypogonadotropic hypogonadism patients (13 women) by immunofluorometric methods (hLH-Spec and hFSH-Spec, AutoDELFIA, Wallac Oy, Turku, Finland). RESULTS: The genetic variant of the luteinizing hormone beta-subunit gene was present at a similar frequency in healthy subjects (14.4%) compared to patients with hypogonadotropic hypogonadism (16.6%). There was no effect of the allelic variant of the luteinizing hormone beta-subunit gene on luteinizing hormone levels in patients with hypogonadotropic hypogonadism as compared to healthy subjects. CONCLUSION: This study indicates that the allelic variant Trp8Arg/Ile15Thr of the luteinizing hormone beta-subunit gene is a common polymorphism in the Brazilian population (14.4%). The same frequency of this luteinizing hormone variant in the groups with hypogonadotropic hypogonadism and in the healthy subjects excludes a relationship between this variant and hypogonadotropic hypogonadism.

Adult↗

Effect of dietary lipid on lutein metabolism during aflatoxicosis in young broiler chickens.

The effect of concentration of dietary fat on pigmentation of broiler chickens was investigated in diets containing: 1) 0 or 1.4 micrograms of aflatoxin and 35 micrograms of lutein/kcal of diet; and 2) different levels of dietary fat (0, 2, 4, 6, 8, or 10% cottonseed oil). Serum lutein and its metabolite, 3'-oxolutein, increased with increasing dietary fat until it reached a plateau at 6% fat. Aflatoxin significantly (P less than .05) lowered serum lutein and 3'-oxolutein at all levels of fat. Dietary fat and aflatoxin interacted significantly (P less than .05), with the effect of aflatoxin being greater at the low levels of fat than at the high fat levels. In the toe webs of the birds, the concentrations of lutein and its metabolites, lutein monoester, lutein diester, and 3'-oxolutein responded similarly to aflatoxin and to dietary fat, except that increasing the amount of dietary fat did not spare the effect of aflatoxin on 3'-oxolutein. The effect of chain length and the saturation of fatty acids on the absorption of lutein during aflatoxicosis was investigated in a factorial design for aflatoxin (0 and 4 micrograms/g of diet) and seven fatty acids at 5% of the diet. In control birds, lutein absorption was promoted by lauric = oleic greater than capric = linoleic greater than myristic greater than palmitic = stearic acids. Aflatoxin significantly (P less than .05) depressed the absorption of lutein regardless of the fatty acid present.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Human chorionic gonadotropin stimulation of relaxin secretion by luteinized human granulosa cells.

OBJECTIVE: To determine the effect of human chorionic gonadotropin (hCG) on relaxin secretion by long-term cultures of luteinized human granulosa cells (GC). DESIGN: Luteinized human GC were collected from 10 women undergoing in vitro fertilization (IVF) cycles. Luteinized human GC from each woman were plated in replicate wells at 1 x 10(5) cells/well and exposed to medium 199 (GIBCO, Grand Island, NY), medium 199 with 1 IU/mL hCG, and/or medium 199 with 100 IU hCG/mL. Luteinized human GC were maintained for up to 40 days in culture. Spent media were changed every 2 days and assayed for relaxin and progesterone (P) at the conclusion of each experiment. SETTING: Tertiary care center. PATIENTS, PARTICIPANTS: Luteinized human GC were obtained from women undergoing controlled ovarian hyperstimulation for IVF with one of the following regimens: (1) clomiphene citrate with human menopausal gonadotropins (hMG); (2) hMG alone; or (3) hMG with leuprolide acetate. All women were less than 40 years of age, in good health, and were not taking medications other than those used in the ovulation-induction regimen. MAIN OUTCOME MEASURES: Levels of P and relaxin in spent media. RESULTS: Relaxin secretion by luteinized human GC was dependent on hCG stimulation and was detected only after a time lag in culture. After relaxin secretion was detected, it was maintained throughout the culture period (10 to 22 days). Luteinized human GC produced P immediately under both basal and stimulated conditions. Progesterone production continued throughout the culture period with hCG-stimulated cells producing significantly greater P after 4 to 8 days in culture. CONCLUSIONS: Luteinized human GC obtained at the time of oocyte retrieval secrete relaxin in response to hCG stimulation and secrete P under both basal and hCG-stimulated conditions, thereby serving as a model to explore luteal function and control.

Adult↗

Modulatory actions of luteinizing hormone-releasing hormone on electrical activity of preoptic neurons in brain slices.

Single unit activity was recorded from 378 neurons, in two preoptic nuclei rich in luteinizing hormone-releasing hormone neurons, using in vitro brain tissue slices which were prepared form either ovariectomized or ovariectomized plus estradiol-treated rats. To test possible transmitter-like actions, agents were injected into the perfusion medium. Luteinizing hormone-releasing hormone excited 46%, inhibited 7%, and evoked biphasic responses in 2% of the 250 units tested. By comparison, two other peptides, thyrotropin-releasing hormone and cholecystokinin-octapeptide sulfated were exclusively excitatory, acting on 55 and 67% of the neurons, respectively. The response to thyrotropin-releasing hormone, cholecystokinin-octapeptide sulfated, and neurotransmitters were prompt, large, and consistent from trial to trial. In contrast, responses to luteinizing hormone-releasing hormone were usually delayed, small, and variable. Responses to the agents tested were not affected by in vivo estradiol treatment. Possible modulatory actions of luteinizing hormone-releasing hormone were tested by comparing the responses of single neurons to norepinephrine and serotonin before and after an application of luteinizing hormone-releasing hormone. In 39 and 20% of the 119 neurons tested, the norepinephrine responses were potentiated and attenuated, respectively, by luteinizing hormone-releasing hormone. In 46 serotonin-responsive neurons, 28% were potentiated and 22% attenuated. These neuromodulatory actions of luteinizing hormone-releasing hormone were specific in affecting only certain responses of certain neurons, and they were not duplicated on the same neurons by thyrotropin-releasing hormone. It appears that luteinizing hormone-releasing hormone may be a neuromodulator in the preoptic area.

Action Potentials↗

Targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207 inhibits growth of OV-1063 human epithelial ovarian cancers in nude mice.

OBJECTIVE: The aim of the study was to investigate the effects of the cytotoxic analog of luteinizing hormone-releasing hormone AN-207 on the growth of the OV-1063 human epithelial ovarian cancers, which express luteinizing hormone-releasing hormone receptor. AN-207 consists of doxorubicin derivative 2-pyrrolinodoxorubicin (AN-201) linked with the carrier [D-lysine6 ]luteinizing hormone-releasing hormone. STUDY DESIGN: Female nude mice bearing xenografts of OV-1063 ovarian cancers were treated with analog AN-207, cytotoxic radical AN-201, or agonist [D-lysine6 ]luteinizing hormone-releasing hormone. The levels and expression of messenger ribonucleic acid of receptors for luteinizing hormone-releasing hormone and epidermal growth factor were evaluated. RESULTS: The growth of OV-1063 tumor was significantly inhibited by 3 to 5 nmol AN- 207 but not by [D-lysine6 ]luteinizing hormone-releasing hormone. Cytotoxic radical AN-201 was toxic at these doses. After treatment with AN-207 receptors for luteinizing hormone-releasing hormone were not detectable, epidermal growth factor receptor levels declined, and expressions of their respective messenger ribonucleic acids were decreased. CONCLUSIONS: Targeted cytotoxic luteinizing hormone-releasing hormone analog AN-207 is less toxic than equimolar doses of its radical 2-pyrrolinodoxorubicin and effectively inhibits ovarian tumor growth. Targeted chemotherapy may improve management of ovarian cancer.

Animals↗

Premature luteinization in controlled ovarian hyperstimulation has no adverse effect on oocyte and embryo quality.

OBJECTIVE: To determine if premature luteinization has an adverse effect on oocyte and, hence, embryo quality. DESIGN: Retrospective evaluation of anonymous ovum donors/oocyte recipients. SETTING: A large oocyte donation program. PATIENTS, PARTICIPANTS: Sixty-eight women undergoing controlled ovarian hyperstimulation (COH) as ovum donors were matched to 68 women with ovarian failure as ovum recipients who had endometrial maturation exogenously controlled by an identical hormone replacement protocol. INTERVENTIONS: Serum was collected for E2 and P in donors and recipients. MAIN OUTCOME MEASURES: The incidence of premature luteinization was determined in donors. Cycle characteristics were compared between donors with and without premature luteinization, with emphasis on oocyte and embryo quality. Implantation rates per embryo and delivery rates per transfer were measured in recipients. RESULTS: Twenty-one (31%) of the donors demonstrated premature luteinization. Serum P was higher on day before hCG, day of hCG, and day after hCG in women demonstrating premature luteinization. However, there were no differences between donor cycles with or without premature luteinization as determined by donor age, ampules of gonadotropins used, day of hCG administration, peak E2, total number of oocytes, and number of mature oocytes retrieved. Ovum recipients were of similar age and had similar E2 exposure (area under the E2 curve) before P administration. Similar fertilization rates, incidence of polyspermia, number of embryos transferred of similar embryo grade, and similar implantation rates and deliveries per transfer were observed in women receiving oocytes from donors with and without premature luteinization, respectively. CONCLUSIONS: Similar oocyte quality, fertilization, and polyspermia rates, embryo quality, implantation, and delivery rates suggest that any negative impact of premature luteinization on pregnancy rates in COH cycles from young women is not due to an adverse effect of PL on oocyte and hence embryo quality, but rather on the endometrial environment.

Chorionic Gonadotropin↗

Caffeine and carbonyl cyanide m-chlorophenylhydrazone increased evoked and spontaneous release of luteinizing hormone-releasing hormone from intact presynaptic terminals.

In bullfrog sympathetic ganglia, the ryanodine-sensitive Ca2+ store and mitochondria modulate [Ca2+] within nerve terminals. We used caffeine (10 mM) and carbonyl cyanide m-chlorophenylhydrazone (10 microM) to assess how these Ca2+ stores affect release of a neuropeptide, luteinizing hormone-releasing hormone, from these nerve terminals. Release of luteinizing hormone-releasing hormone was evoked by electrical stimulation to presynaptic nerves and was monitored as a late slow excitatory postsynaptic potential in ganglionic neurons. Caffeine increased release of luteinizing hormone-releasing hormone similarly whether the release was evoked by 4 or 20 Hz stimulations (by 2.7 +/- 1.1- and 3.2 +/- 0.9-fold, mean +/- S.E.M., n = 27, respectively). Carbonyl cyanide m-chlorophenylhydrazone augmented release of luteinizing hormone-releasing hormone evoked by 4 Hz stimulation much more strongly (by 11.8 +/- 1.8-fold) than it increased the release evoked by 20 Hz stimulation (by 3.6 +/- 1.3-fold, n = 25). We detected spontaneous release of luteinizing hormone-releasing hormone as a slow hyperpolarization in response to a brief application of an antagonist to the receptors for luteinizing hormone-releasing hormone in 65% (34 of 52) and 39% (11 of 28) of the ganglionic B and C neurons, respectively. Caffeine increased spontaneous release of luteinizing hormone-releasing hormone by 2.3 +/- 0.7-fold (n = 6) whereas carbonyl cyanide m-chlorophenylhydrazone increased this release by 4.27- and 1.76-fold (n = 2). Facilitation of Ca2+ release from the intracellular store by caffeine and inhibition of mitochondrial Ca2+ removal by carbonyl cyanide m-chlorophenylhydrazone increased spontaneous as well as evoked release of luteinizing hormone-releasing hormone. Moreover, caffeine increments of evoked release did not depend on the firing frequency of the nerve whereas carbonyl cyanide m-chlorophenylhydrazone augmentations of evoked release strongly depended on the firing frequency.

Acetylcholine↗

OBSERVATIONS ON THE FINE STRUCTURE OF LUTEIN CELLS. II. THE EFFECTS OF HYPOPHYSECTOMY AND MAMMOTROPHIC HORMONE IN THE RAT.

Corpus luteum formation was induced in 26-day-old rats which were subsequently hypophysectomized and injected with mammotrophic hormone (MH, LTH). Sections of corpora lutea from these animals were examined with the electron microscope and compared with similarly prepared (Caulfield's fixed, Araldite embedded) corpora from normal pregnancy and from controls, the latter consisting of corpora prior to hypophysectomy and corpora from uninjected rats 7 to 14 days after hypophysectomy. Lutein cells from corpora lutea of injected animals and of normal pregnancy are characterized by abundant, tortuous, tubular agranular endoplasmic reticulum and by mitochondria, many of which are disc-shaped with dense matrices and both villiform and lamelliform cristae. The endoplasmic reticulum is most abundant in lutein cells from pregnant animals, in which cells it is in the form of thin, highly tortuous tubules. The form of the lipid droplets seen in cells of stimulated animals varies greatly. Marginal foldings of the lutein cells on the perivascular space were found in all instances. Lutein cells from hypophysectomized animals have a less highly developed agranular endoplasmic reticulum. The mitochondria have irregular outlines and a relatively lucid matrix. The lipid droplets in these cells show less tendency to be extracted, but are not so large or abundant as in the cells of onset controls. Granules believed to contain lipid pigments are common in the lutein cells of these control animals. It is suggested that lutein cells from corpora lutea which are actively secreting progesterone may be readily distinguished from lutein cells from non-active corpora by means of the multiple characteristics enumerated. It is further suggested that mammotrophic hormone has a general effect on the metabolism of lutein cells rather than solely affecting a specific organelle, the abundance or composition of which may be the limiting factor in the production of progesterone.

Animals↗

Transcriptional regulation of the cyclooxygenase-2 gene changes from protein kinase (PK) A- to PKC-dependence after luteinization of granulosa cells.

This study was designed to elucidate the molecular mechanism(s) mediating cyclooxygenase-2 (Cox-2) regulation during differentiation of the granulosa cell. The 5' flanking sequence of the Cox-2 gene was linked to a vector with a luciferase reporter gene, and this vector was transfected into freshly isolated bovine granulosa cells or granulosa cells after culture with or without forskolin to induce luteinization in vitro. The Cox-2 promoter was inducible by 8-bromo cAMP but not by phorbol esters in fresh granulosa cells, and maximal expression by cAMP was delayed until 48 h after treatment. In contrast, after luteinization of granulosa cells by 8-day treatment with forskolin, the Cox-2 promoter was immediately inducible by phorbol esters but not by cAMP. In granulosa cells cultured for 8 days without forskolin, the Cox-2 promoter continued to be inducible only by cAMP and not by phorbol esters. Unexpectedly, no delay was observed in the induction of Cox-2 by cAMP in granulosa cells that were cultured without forskolin, compared with an approximately 1 day delay in Cox-2 induction by cAMP in fresh granulosa cells. Myristoylated protein kinase (PK) A and PKC inhibitory peptides were utilized to further confirm the PKA- or PKC-dependence of Cox-2 induction. Time-course experiments showed that only 2 days of forskolin treatment could induce PKC-responsiveness of the Cox-2 promoter, although maximal responsiveness was not observed until 10 days of luteinization. Promoter activity was also analyzed in a series of deletion mutants as well as site-directed mutants of C/EBP, CRE, and E-box. A 282-base pair sequence in the Cox-2 5' flanking region maintained full inducibility by PKA in granulosa cells and by PKC in luteinized granulosa cells. The E-box element was found to be the critical regulatory element for Cox-2 induction by either PKA in granulosa cells or by PKC in luteinized granulosa cells. Electrophoretic mobility shift assays were performed on nuclear extracts from fresh or luteinized granulosa cells. Upstream stimulatory factor (USF)-1 and USF-2 bound to the E-box of the Cox-2 gene, and binding was similar for nuclear extracts from fresh, cultured, or luteinized granulosa cells. Thus, although luteinization changes transcriptional regulation of Cox-2 from PKA- to PKC-dependence, the crucial role of the E-box element in this transcriptional activation is conserved.

5' Untranslated Regions↗

Expression of adrenomedullin by human granulosa lutein cells and its effect on progesterone production.

OBJECTIVE: Adrenomedullin (AM) has diverse functions and is expressed in a variety of tissues. This study was conducted to investigate the expression of AM in the human ovary and its effect on progesterone production by human granulosa lutein cells. DESIGN AND METHODS: Follicular fluid and blood samples were obtained at the time of oocyte retrieval from patients undergoing in vitro-fertilization cycles. Concentrations of AM in follicular fluid and plasma were measured by RIA. Granulosa cells were isolated from follicular fluid and expression of AM mRNA was examined by RT-PCR. Granulosa lutein cells were cultured in vitro and secretion of AM by those cells was determined by immunoprecipitation followed by PAGE. Immunohistochemical staining with human ovaries was carried out, using a specific antibody to AM. Furthermore, the effect of AM on progesterone production by cultured granulosa lutein cells was studied. RESULTS: Concentrations of AM in follicular fluid collected just before ovulation were significantly higher than those in the plasma (P<0.01). AM mRNA was expressed in granulosa cells at the preovulatory stage. Cultured granulosa lutein cells secreted immunoreactive AM. With immunohistochemical staining, it was revealed that AM was most abundantly expressed in granulosa lutein cells at the midluteal phase. No appreciable staining for AM was observed in granulosa cells in primordial and preantral follicles, whereas immunolocalization of AM was noted in granulosa cells of dominant follicles although it was not as prominent as in granulosa lutein cells at the midluteal phase. Furthermore, addition of AM to cultured granulosa lutein cells augmented progesterone secretion in a dose-dependent manner. CONCLUSIONS: These results suggest that AM is transcribed and secreted in human granulosa lutein cells as a local factor to enhance progesterone production by those cells.

Adrenomedullin↗

Analysis of brain neuropeptides by capillary electrophoresis: determination of luteinizing hormone-releasing hormone from ovine hypothalamus.

The use of capillary electrophoresis to analyze in vivo release of luteinizing hormone-releasing hormone from the ewe median eminence and tissue content of luteinizing hormone-releasing hormone from discrete brain areas (within and immediately adjacent to the median eminence) is described. Results were compared with those obtained with a specific luteinizing hormone-releasing hormone radioimmunoassay. In vivo release samples were obtained by a push-pull cannula procedure. The exact position of the median eminence in each animal was determined from lateral roentgenographs after infusion of a radiopaque dye into the third ventricle. Each ewe median eminence was perfused with an artificial cerebrospinal fluid solution and sampled at 20-min intervals. Brain tissues for luteinizing hormone-releasing hormone content were obtained after each animal was killed. Samples were either analyzed by capillary electrophoresis and UV detection at 210 nm or assayed with a specific luteinizing hormone-releasing hormone radioimmunoassay. Tissue homogenate content and release samples had several peaks resolved by capillary electrophoresis and UV detection. Luteinizing hormone-releasing hormone was identified as one of these peaks. Luteinizing hormone-releasing hormone was also shown to be present in these samples when evaluated by radioimmunoassay. A good correlation between capillary electrophoresis and radioimmunoassay was observed for luteinizing hormone-releasing hormone content values obtained from discrete hypothalamic areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Kinetics of 14C distribution after tracer dose of 14C-lutein in an adult woman.

Lutein is an oxygenated carotenoid (xanthophyll) found in dark green leafy vegetables. High intakes of lutein may lower the risk of age-related macular degeneration. Current understanding of human lutein metabolism as it might occur in vivo is incomplete. Therefore, we conducted a feasibility study where we dosed a normal adult woman with 14C-lutein (125 nmol, 36 nCi 14C), dissolved in olive oil (0.5 g/kg body weight) and mixed in a banana shake. Blood, urine, and feces collected before the dose was administered served to establish baseline values. Thereafter, blood was collected for 63 d following the dose, while feces and urine were collected for 2 wk post-dose. The 14C contents in plasma, urine, and feces were measured by accelerator MS. The 14C first appeared in plasma 1 h after dosing and reached its highest level, approximately2.08% of dose/L plasma, at 14 h post-dose. The plasma pattern of 14C did not include a chylomicrons/VLDL (intestinal) peak like that when the same subject received 14C-beta-carotene (a previous test), suggesting that lutein was handled differently from beta-carotene by plasma lipoproteins. Lutein had an elimination half-life (t1/2) of approximately10 d. Forty-five percent of the dose of 14C was eliminated in feces and 10% in urine in the first 2 d after dosing. Quantifying human lutein metabolism is a fertile area for future research.

Administration, Oral↗

The effect of acute exercise on pulsatile release of luteinizing hormone in women runners.

Endurance exercise has been associated with reproductive dysfunction. We have previously suggested that pulsatile release of luteinizing hormone is impaired at rest in normal menstruating runners compared with sedentary women. To determine whether acute exercise had any effect on pulsatile release of luteinizing hormone we investigated serum luteinizing hormone levels in six normal menstruating runners at rest and after 60 minutes of running exercise. Exercise induced an increment in circulating luteinizing hormone levels greater than the change in hematocrit. The luteinizing hormone pulse frequency, calculated as the number of luteinizing hormone pulses per 6 hours, was reduced after exercise compared with values obtained at rest. There was no significant difference in pulse amplitude or area under the 6-hour curve between resting and postexercise situations. These data suggest that acute exercise has an inhibitory effect on luteinizing hormone pulsatile release at the hypothalamic level in eumenorrheic runners that is in addition to the previously described effect of training.

Adult↗

The accuracy of urinary luteinizing hormone testing in predicting ovulation.

Transvaginal ultrasonography and daily urinary luteinizing hormone testing were used to evaluate the accuracy of urinary luteinizing hormone testing in predicting ovulation in 33 spontaneously ovulating women beginning on cycle day 10. Ovulation was confirmed in all patients with luteal phase progesterone levels and endometrial biopsy specimens. The results demonstrated that transvaginal ultrasonography and urinary luteinizing hormone testing detected ovulation in all cycles. However, the onset of urinary luteinizing hormone occurred after follicle rupture was documented by ultrasonography in 9% of the women studied. Thus the question of accuracy of urinary luteinizing hormone testing in prediction contrasted to detection of ovulation is raised. This observation is of importance in patients in whom prediction of ovulation is critical to treatment management. Therefore, an ultrasonographic examination to confirm the presence of an unruptured follicle on the day of onset of urinary luteinizing hormone surge is recommended, particularly in patients failing to conceive after three to six cycles of artificial insemination when the inseminations are timed with the onset of urinary luteinizing hormone surge.

Adult↗

Steroid biosynthesis in the Sertoli-Leydig cell tumor: effects of insulin and luteinizing hormone.

In vitro steroid production by a virilizing Sertoli-Leydig cell tumor of the ovary was studied. For comparison, stromal tissue from the opposite normal ovary was also incubated under similar conditions. The tumor fragments secreted significantly more testosterone (527 +/- 168 versus 48 +/- 29 pg/mg tissue, p less than 0.001), androstenedione (1188 +/- 400 versus 40 +/- 10 pg/mg tissue, p less than 0.001), and dehydroepiandrosterone (419 +/- 132 versus 73 +/- 25 pg/mg tissue, p less than 0.004) than that of normal ovarian stroma. Measurement of steroids in the ovarian venous serum draining the tumor indicated a peripheral ovarian gradient for both delta 4 and delta 5 steroids. Incubation of tumor fragments with luteinizing hormone alone resulted in a significant increase in the secretion of androstenedione and dehydroepiandrosterone (p less than 0.05). Addition of insulin to luteinizing hormone resulted in significantly greater release of androstenedione than that of treatment with luteinizing hormone alone (p less than 0.04). Addition of insulin had no effect on the release of dehydroepiandrosterone. Luteinizing hormone and insulin, either alone or in combination, failed to produce any change in the secretion of testosterone. We conclude that (1) increased testosterone secretion by Sertoli-Leydig cell tumor resulted from increased availability of precursors from both delta 4 and delta 5 pathways; (2) the tumor was responsive to luteinizing hormone with an increase in the secretion of androstenedione and dehydroepiandrosterone; (3) insulin acts synergistically with luteinizing hormone to increase secretion of androstenedione; (4) the tumor has specific binding sites for insulin; and (5) the increased levels of insulin and luteinizing hormone in polycystic ovarian disease may play a role in the pathogenesis of Sertoli-Leydig cell tumor.

Adult↗