The ovarian renin-angiotensin system in polycystic ovarian syndrome.
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Animals↗
Biomedical subjects
F Naftolin
Publications and source records attributed to F Naftolin.
The role of estradiol and progesterone in phased synaptic remodelling of the rat arcuate nucleus.
During the estrous cycle there is a phasic synaptic remodelling in the hypothalamic arcuate nucleus, consisting in a loss and regain of axo-somatic synapses during the 48 h period between the morning of proestrus and the morning of metestrus. Synaptic changes are accompanied by cyclic modifications in the number of intramembrane particles in the plasma membrane of arcuate neuronal somas. To test the effect of the ovarian steroids on arcuate axo-somatic synapses we treated castrated females either with oil vehicle, 17 beta-estradiol, progesterone, or a combination of estradiol and progesterone, and observed them for 48 h. The number of axo-somatic synaptic profiles showed a 33% fall by 24 h after estradiol treatment and returned to control levels by 48 h. The effect of estradiol on axo-somatic synapses was accompanied by a marked and reversible modification of the number of intramembrane particles in the plasma membrane of arcuate neuronal somas. Progesterone alone did not affect the number of axo-somatic synaptic profiles nor the number of intramembrane particles, but when administered together with estradiol, blocked the effects of estradiol on neuronal membrane and synapses.
Animals↗
Natural fluctuation and gonadal hormone regulation of astrocyte immunoreactivity in dentate gyrus.
The number and the surface density of cells immunoreactive for the specific astrocytic marker glial fibrillary acidic protein (GFAP), were evaluated in both the hilus of the dentate gyrus and the granular layer of the vermis of the cerebellar cortex of adult female rats during the different phases of the estrous cycle, after ovariectomy and after the pharmacological administration of estradiol and/or progesterone to ovariectomized rats. Although no significant differences were detected in the number of immunoreactive cells among the different experimental groups studied, their surface density showed significant changes in the hilus of the dentate gyrus. The surface density of immunoreactive cells was increased in the afternoon of proestrus and on the morning of estrus compared to the morning of proestrus, diestrus, and metestrus, was decreased after ovariectomy, and showed a dose-dependent increase in ovariectomized rats injected with 17 beta estradiol (1, 10, or 300 micrograms/rat), alone or in combination with progesterone (500 micrograms/rat). In contrast, it was not affected by the administration of 17 alpha estradiol (300 micrograms/rat). The surface density of immunoreactive cells was significantly increased over control values by 5 h after the injection of 17 beta estradiol (300 micrograms/rat) and as early as 1 h after the administration of progesterone. The separate injection of either 17 beta estradiol or progesterone had smaller effects on the surface density of immunoreactive cells than did the administration of both hormones together. The surface density of GFAP-immunoreactive cells reached maximal values by 24 h after the administration of 17 beta estradiol and/or progesterone and returned to control levels by 48 h after the combined injection of progesterone and 17 beta estradiol, while in the rats that were injected with only one of the two hormones, the surface density of immunoreactive cells remained over control values for at least 9 days. No such hormonal effects on GFAP-immunoreactive cells were observed in the cerebellar cortex.
Animals↗
Cycloheximide mimics effects of oestradiol that are linked to synaptic plasticity of hypothalamic neurons.
The synaptic connectivity of the rat arcuate nucleus, a hypothalamic area rich in oestradiol receptors, is rapidly affected by physiological modifications of hormonal levels. A rise of oestradiol in plasma elicits a coordinated neuronal-glial response that begins with a rapid fall in the number of small (< 10 nm) intramembrane particles and a rapid increase in the number of large (> 10 nm) intramembrane particles in neuronal membranes, followed by a modification in the branching of astrocytic processes and finally results in decreased number of axo-somatic synapses and increased glial wrapping of the neuronal somas. In the course of a series of studies aimed to test possible non-genomic effects of oestradiol on neuronal membranes we analyzed the effect of the systemic administration of the protein synthesis inhibitor cycloheximide on the ultrastructure of arcuate neurons and granule cells of the cerebellar cortex, an area of the brain with low levels of estrogen receptors. Cycloheximide resulted in a significant inhibition of protein synthesis in hypothalmus and cerebellum of ovariectomized rats. Under these circumstances, the number of small intramembrane particles was reduced in hypothalamic and cerebellar neuronal membranes while the number of large intramembrane particles showed a decrease in cerebellar membranes and a transient increase in arcuate neuronal somas. Furthermore, cycloheximide resulted in an increased glial wrapping of arcuate neuronal somas but not of cerebellar granule cells. The ensheathing of arcuate neurons by glial was associated with a 41% decrease in the number of axo-somatic synapses. These results indicate that the protein synthesis inhibitor cycloheximide may elicit the integrated neuronal-glial response that is associated with the hormonally induced remodelling of synaptic contacts on arcuate neurons.
Animals↗
Proliferative index of human luteinized granulosa cells varies as a function of ovarian reserve.
OBJECTIVE: We examined whether the proliferative index of luteinized granulosa cells, as determined by flow cytometry, varied as a function of a woman's ovarian reserve, as reserve, as reflected by follicular-phase day 3 serum follicle-stimulating hormone. STUDY DESIGN: This prospective cohort study consisted of 19 women of similar chronologic age preparing for in vitro fertilization-embryo who met specific day 3 serum follicle-stimulating hormone criteria. The "low follicle-stimulating hormone" group consisted of 11 women with day 3 serum follicle-stimulating hormone levels < or = 6 IU/L. The "high follicle-stimulating hormone" group consisted of eight women with day 3 serum follicle-stimulating hormone levels > or = 18 IU/L. A total of 56 preovulatory follicles containing > or = 10(4) luteinized granulosa cells were examined by flow cytometry. The low follicle-stimulating hormone group was compared with the high follicle-stimulating hormone group to examine proliferative index as a function of serum day 3 follicle-stimulating hormone levels. RESULTS: The low follicle-stimulating hormone group had a greater proliferative index (11.1% +/- 0.4%) than did the high follicle-stimulating hormone group (8.3% +/- 0.6%), p < 0.001). This study demonstrates that in spite of the same chronologic age, luteinized granulosa cells from preovulatory follicles of women with day 3 serum follicle-stimulating hormone levels > or = 18 IU/L have a 25% decreased proliferative index compared with luteinized granulosa cells from women with day 3 serum follicle-stimulating hormone levels < or = 6. CONCLUSIONS: This suggests that granulosa cell proliferation is influenced by ovarian reserve and may explain in part the more favorable response to ovulation induction protocols that younger women demonstrate compared with women of more advanced reproductive age.
Adult↗
Aromatase immunoreactivity in the rat brain: gonadectomy-sensitive hypothalamic neurons and an unresponsive "limbic ring" of the lateral septum-bed nucleus-amygdala complex.
The aromatase (estrogen synthetase) enzyme catalyzes the conversion of androgens to estrogens in peripheral tissues, as well as in the brain. Our study aimed at comparing the brain distribution of aromatase-immunoreactive neurons in male and female, normal and gonadectomized rats. Light microscopic immunostaining was employed using a purified polyclonal antiserum raised against human placental aromatase. Two anatomically separate aromatase-immunoreactive neuronal systems were detected in the rat brain: A "limbic telencephalic" aromatase system was composed by a large population of labeled neurons in the lateral septal area, and by a continuous "ring" of neurons of the laterodorsal division of the bed nucleus of stria terminalis, central amygdaloid nucleus, stria terminalis, and the substantia inominata-ventral pallidum-fundus striati region. The other, "hypothalamic" aromatase system consisted of neurons scattered in a dorsolateral hypothalamic area including the paraventricular, lateral and dorsomedial hypothalamic nuclei, the subincertal nucleus as well as the zona incerta. In addition, a few axon-like processes (unresponsive to gonadectomy) were present in the preoptic-anterior hypothalamic complex, the ventral striatum, and midline thalamic regions. No sexual dimorphism was observed in the distribution or intensity of aromatase-immunostaining. However, 3 days, 2, 3, 8, 16, or 32 weeks after gonadectomy, aromatase-immunoreactive neurons disappeared from the hypothalamus, whereas they were still present in the limbic areas of both sexes. The results indicate the existence of two distinct estrogen-producing neuron systems in the rat brain: (1) a "limbic ring" of aromatase-labeled neurons of the lateral septum-bed nucleus-amygdala complex unresponsive to gonadectomy; and (2) a sex hormone-sensitive "hypothalamic" aromatase neuron system.
Amygdala↗
Pseudoaromatase in circulating lymphocytes.
A variety of data suggesting a relationship between estrogens and the immune system prompted a study of aromatase activity in blood lymphocytes. A tritiated water aromatase assay detected activity of 1.9 to 25.1 pmol/g protein/h in 14 samples of human lymphocytes. To confirm these results, additional tritiated water and product isolation assays were performed on a large pool of lymphocytes obtained from 4 U of blood. An assay using [1 beta-3H]androstenedione generated high apparent aromatase activity, 943 pmol/g protein/h, but this activity could not be blocked by the aromatase inhibitor, CGS 16949A. More direct methods of evaluation yielded the following results: (1) PCR demonstrated no aromatase mRNA production in lymphocytes; (2) direct product isolation using [1,2,6,7-3H]androstenedione yielded insignificant production of estrone and estradiol; (3) immunostaining of fixed lymphocyte smears with a polyclonal antibody to aromatase yielded equivocal results. These data suggest the presence of pseudoaromatase in blood lymphocytes. Since circulating lymphocyte pseudoaromatase levels can be correlated with various factors in patients, such as age, menopausal status, and glucose ingestion, further studies of this activity are warranted.
Androstenedione↗
Immunohistochemical localization of renin and angiotensin in the ovary: comparison between normal women and patients with histologically proven polycystic ovarian disease.
OBJECTIVE: This study was designed to test the hypothesis that the ovarian renin-angiotensin system may play a role in polycystic ovarian disease (PCOD). DESIGN: The immunohistochemical distribution of renin and angiotensin in ovaries from seven women with histologic diagnosis of PCOD was compared with that of normal ovaries. RESULTS: The large cystic follicles of polycystic ovaries (PCO) presented intense immunostaining for renin and angiotensin in both theca and granulosa cells (GCs). In developing follicles of normal ovaries, the immunostaining was restricted to the theca cell layer, with the exception of the immediately preovulatory follicles which displayed intense positivity of granulosa as well as theca cells. Atretic follicles of normal ovaries showed staining of both theca and GCs. In both normal and PCO, patches of hilus cells were intensely stained. Luteal cells also consistently stained both in normal ovaries and in the occasional corpus luteum present in polycystic ovaries. CONCLUSIONS: This study highlights the link between the ovarian renin-angiotensin system and those ovarian compartments known to be actively engaged in androgen secretion and/or luteinization and suggests that there may be an association between the ovarian renin-angiotensin system and PCOD.
Adult↗
A phytoestrogen diet induces the premature anovulatory syndrome in lactationally exposed female rats.
The effects of a phytoestrogen diet on sexual differentiation were examined in lactationally exposed rat pups. Rat dams were provided a semipurified diet containing the isoflavonoid coumestrol at a concentration (0.01%) previously found to be uterotrophic. Coumestrol treatment did not significantly alter the time of vaginal opening, although vaginal opening did occur at a lighter body weight. By 132 days of age, 83% of coumestrol-treated females exhibited the cornified smears of a persistent estrous state. By contrast, 91% of control animals were cycling regularly at 132 days of age. Estradiol stimulation failed to elicit an LH elevation in the coumestrol-treated animals, suggesting the possibility of neuroendocrine impairments. These findings indicate that the female offspring of mothers fed a low-level phytoestrogen diet during lactation manifest early and nearly universal disruption of cyclicity of the persistent-estrus type.
Animals↗
Luteinizing hormone-releasing hormone and gamma-aminobutyric acid neurons in the medial preoptic area are synaptic targets of dopamine axons originating in anterior periventricular areas.
The aim of this study was to characterize further the transmitter content and the location of the parent cells of tyrosine hydroxylase-immunoreactive boutons terminating on luteinizing hormone-releasing hormone- and glutamic acid decarboxylase-immunoreactive neurons in the rat medial preoptic area. Electron microscopic immunostaining for luteinizing hormone-releasing hormone, tyrosine hydroxylase or glutamic acid decarboxylase was performed on desipramine-pretreated (to protect norepinephrine and epinephrine axons) rats which received a stereotaxic injection of 6-hydroxydopamine into the medial preoptic area anteroventral periventricular nucleus 48 h prior to sacrifice. This treatment induced acute degeneration of dopamine axon terminals characterized by the development of autophagous cytolysosomes, an early morphological sign of catecholamine axon degeneration. To further define the cells of origin of these dopamine boutons, the anterograde marker Phaseolus vulgaris leucoagglutinin was iontophoretically applied to the zona incerta. Six days later, rats received a 6-hydroxydopamine injection into the zona incerta or the lateral ventricle, and 48 h later, double immunostaining was performed for Phaseolus vulgaris leucoagglutinin and tyrosine hydroxylase, luteinizing hormone-releasing hormone, or glutamic acid decarboxylase on preoptic area vibratome sections. Following the 6-hydroxydopamine injection into the anteroventral periventricular nucleus, autophagous cytolysosome-containing degenerated axons were found in synaptic contact with both luteinizing hormone-releasing hormone and GABA neurons in the medial preoptic area, confirming that these are dopaminergic connections. Following the double injection treatment, 6-hydroxydopamine-induced degenerated, Phaseolus vulgaris leucoagglutinin-labeled dopamine axons originating in the zona incerta were not found to contact luteinizing hormone-releasing hormone-containing or GABA cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Estrogen induces synaptic plasticity in adult primate neurons.
The number of axosomatic synapses, the length of the synaptic plates and the perimeter of the post synaptic neuronal perikarya were assessed on thin sections from the infundibular hypothalamic nucleus and from the ventrobasal thalamus of 3 adult ovariectomized African green monkeys that were treated with estradiol valerate and of 3 control animals that were injected with vehicle. Estradiol valerate treatment resulted in a 61% [corrected] decrease in the number of axosomatic synapses in the infundibular hypothalamic nucleus. The length of the synaptic plates and the perimeter of the postsynaptic cells were not affected by the hormonal treatment. The decrease in the number of axosomatic synaptic inputs in the infundibular hypothalamic nucleus was accompanied by a significant increase in the glial ensheathing of neuronal somas. No effect of the hormonal treatment was detected in the ventrobasal thalamus. The results indicate that estrogen may induce glial and synaptic plasticity in the hypothalamus of adult primates.
Animals↗
High-grade endometrial carcinoma in tamoxifen-treated breast cancer patients.
PURPOSE: Several reports have associated tamoxifen administration with endometrial carcinoma. A retrospective study of the histologic features of uterine cancer in patients with a history of breast carcinoma was undertaken to determine the effect of treatment with tamoxifen. MATERIALS AND METHODS: A computer search of the Yale-New Haven Hospital Tumor Registry from 1980 to 1990 identified 53 patients with a history of breast carcinoma who subsequently developed a malignant tumor of the uterine corpus. RESULTS: Fifteen patients received tamoxifen for breast carcinoma and 38 did not. The mean ages of the two groups were not significantly different. The mean interval between detection of breast and endometrial cancers was 5 years in the tamoxifen group and 12 years in the nontreated group (P = .0023). Sixty-seven percent of patients in the tamoxifen group had poorly differentiated endometrioid carcinomas (including adenosquamous carcinoma) or carcinomas associated with poor outcome (eg, uterine papillary serous carcinoma, clear-cell carcinoma, or mixed müllerian tumor), as compared with 24% in the nontreated group (P = .03). Patients in the tamoxifen group were much more likely to die of endometrial cancer (33.3% v 2.6% of the nontreated group, P = .005). CONCLUSION: From this retrospective study, it appears that women receiving tamoxifen as treatment for breast cancer who subsequently develop uterine cancer are at risk for high-grade endometrial cancers that have a poor prognosis. These findings also indicate that tamoxifen-associated uterine cancers may have a different basis from those associated with steroidal estrogen treatment.
Adenocarcinoma↗
Neuropeptide-Y innervation of estrogen-induced progesterone receptor-containing dopamine cells in the monkey hypothalamus: a triple labeling light and electron microscopic study.
Light and electron microscopic triple immunostaining was performed on coronal vibratome sections prepared from the hypothalamus of ovariectomized (OVX) and OVX plus estrogen-treated African green monkeys (Cercopithecus aethiops). Immunoreactivity for progesterone receptors (PRs) and neuropeptide-Y (NPY) was visualized by a dark blue to black nickel diaminobenzidine reaction, while the tyrosine hydroxylase-containing perikarya were labeled with a light brown diaminobenzidine reaction. In the OVX plus estrogen-treated material, 30% of the tyrosine hydroxylase-immunoreactive neurons contained PR-immunopositive nuclei. The majority of these cells were found in the central portion of the periventricular area, and a few could be observed in the anterior hypothalamus and the arcuate and dorsomedial hypothalamic nuclei. These tyrosine hydroxylase-immunoreactive PR-containing cells were surrounded with NPY-immunoreactive axon terminals. A correlated electron microscopic analysis of the same sections revealed synaptic contacts between these NPY-immunoreactive boutons and the PR-containing tyrosine hydroxylase-immunoreactive neurons. In contrast, in the OVX animals, no PR-containing tyrosine hydroxylase-immunoreactive neurons could be detected. In these monkeys, the frequency of synaptic contacts between the NPY-immunoreactive axon terminals and tyrosine hydroxylase-immunopositive cells was similar to that in the OVX plus estrogen-treated monkeys. These observations indicate that in a population of hypothalamic dopamine cells, the presence of nuclear PRs is estrogen dependent, show that these cells are innervated by NPY axons, and suggest that these estrogen-induced PR-containing dopamine neurons are involved in mediation of the effect of NPY on hypophyseal hormone secretion, including ovarian steroid hormone-dependent LH and PRL release.
Animals↗
The type 1 angiotensin-II receptor mediates intracellular calcium mobilization in rat luteal cells.
The intracellular cytosolic calcium concentration ([Ca]i) was determined in cultured rat luteal cells using the calcium-chelating dye fura-2 and microspectrofluorimetry. Angiotensin-II (Ang-II) induced a dose-dependent transient increase in [Ca]i (ED50, 9.0 +/- 6.5 nM). After the initial peak in [Ca]i, cytosolic calcium returned to a secondary elevated basal level that was dependent upon the presence of extracellular calcium. Pretreatment of rat luteal cells with Ang-II (100 nM) desensitized a subsequent response to a higher concentration (1 microM), but did not desensitize a prostaglandin F2 alpha (PGF2 alpha)-induced calcium flux. Although the peak increases in [Ca]i induced by Ang-II (1 microM) and PGF2 alpha (10 microM) were not significantly different, the plateau phase stimulated by PGF2 alpha was significantly higher (P < 0.05) than that stimulated by Ang-II (1 microM). Pretreatment of luteal cells with the type 2 Ang-II receptor antagonist PD 123319 (10 microM) did not inhibit calcium mobilization; however, Ang-II (1 microM)-induced calcium mobilization was dose dependently blocked by the type 1 Ang-II receptor antagonist Losartan (DuP 753). The ID50 for Losartan was 5.2 +/- 1.8 nM. Pretreatment of the luteal cells with the endoplasmic reticulum calcium ATPase inhibitor thapsigargin (1 microM) also blocked Ang-II-induced calcium mobilization. These data demonstrate the presence of the type 1 Ang-II receptor in rat luteal cells, through which Ang-II dose dependently mobilizes calcium from an intracellular source, probably the endoplasmic reticulum.
Adenosine Triphosphatases↗
Estramustine and estrone analogs rapidly and reversibly inhibit deoxyribonucleic acid synthesis and alter morphology in cultured human glioblastoma cells.
Estramustine is an estradiol-based agent that has been shown to accumulate in human glioma cells, resulting in a concentration-dependent alteration in cell size and shape within minutes and an inhibition of proliferation over 3 to 6 days. We evaluated human glioblastoma cultures with [3H]thymidine incorporation assays to determine estramustine's early effects on deoxyribonucleic acid synthesis in these tumors. Because estramustine shares a common structural motif with other antimicrotubule drugs, we synthesized four A-ring conjugates of estrone that contained a carbamate moiety but lacked nitrogen mustard. These analogs were examined by [3H]thymidine incorporation and compared with vinblastine. Greater than 70% inhibition of [3H]thymidine incorporation occurred within 1 hour of treatment with estramustine at 10(-5) mol/L, which increased to 80% inhibition at 4 hours. Ethyl carbamate JE208 was nearly as effective as estramustine in inhibiting deoxyribonucleic acid synthesis, and both were more effective than vinblastine. The inhibitory effects of estramustine and estrone analogs were reversible; vinblastine was not reversible. Although estramustine and JE208 induced similar antiproliferative and morphological changes in glioblastoma cells that persisted for at least 4 days, there was a modest recovery of morphology and thymidine incorporation with JE208 after prolonged treatment. The common findings with estramustine and JE208 suggest that these agents may have a similar mechanism of action and form the basis for the investigation of new agents that may rapidly and reversibly inhibit glioblastoma.
Brain Neoplasms↗
The in vitro perifused rat ovary: III. Interrelationship of the follicular and stromal compartments on steroid release.
The preovulatory ovary is composed of two primary tissue components, stroma and follicles. To assess the role of these tissue compartments in ovarian steroidogenesis, stromal tissue, follicular tissue, and a mixture of both tissues from pregnant mare serum gonadotropin (PMSG)-treated, prepubertal rats were perifused simultaneously for 8 h. The basal level of estradiol secretion by stromal tissue was lower (24 +/- 3 pg/mg/30 min), than that secreted by follicles (64 +/- 5.6 pg/mg/30 min, n = 6; p < 0.05). On the other hand, the mean basal levels of progesterone and testosterone secreted by stromal tissue (252 +/- 14 pg/mg/30 min and 162 +/- 18 pg/mg/30 min, respectively) were greater than those secreted by follicular tissue (84 +/- 3 pg/mg/30 min and 81 +/- 4 pg/mg/30 min, respectively). When stromal and follicular tissue were combined the secretion of progesterone, testosterone and estradiol was intermediate to that of the separate tissues. Under gonadotropin stimulation (human menopausal gonadotropins plus follicle stimulating hormone), the follicular tissue secreted greater amounts of steroids than did the stromal tissue, or stromal plus follicular tissue. When stromal tissue and follicular tissue were combined, the levels of basal progesterone and testosterone secreted by both tissues were significantly lower than those of stromal tissue alone. However, the reduction in follicular estradiol secretion induced by stromal tissue under basal conditions, was in large part overcome during gonadotropin perifusion. These observations suggest that locally produced factors may play an inhibitory, paracrine role in the regulation of ovarian steroidogenesis.
Animals↗
The in vitro perifused rat ovary: IV. Modulation of ovarian steroid secretion by insulin.
Insulin has been implicated as a regulatory factor in ovarian steroidogenesis. To assess this issue, we examined the role of insulin on steroid secretion by whole ovaries from pregnant mare serum gonadotropin (PMSG)-pretreated rats, using an in vitro perifusion ovarian model. Three concentrations of insulin were perifused in the absence and presence of gonadotropin pulse-stimulation. Bioactive insulin concentrations after perifusion of ovarian tissue were 4, 40 and 400 mIU/ml. In the absence of gonadotropin-pulse stimulation, acute perifusion with insulin had no effect on ovarian steroid secretion. During stimulation with luteinizing hormone (LH) plus follicle stimulating hormone (FSH), insulin significantly decreased the secretion of testosterone and estradiol but increased the output of progesterone. This effect was only evident after 180 min perifusion and with the highest concentration of insulin. We conclude that acute elevation of insulin concentration has no effect on basal ovarian secretion of progesterone, testosterone, or estradiol in gonadotropin-pretreated rats. However, insulin has a moderate effect on steroid secretion in ovaries exposed to LH/FSH pulsatile stimulation, resulting in a decrease in estradiol and testosterone release, and stimulation of progesterone secretion.
Animals↗
The in vitro perifused rat ovary: V. The significance of the follicle stimulating hormone and luteinizing hormone ratio on steroid release.
In these studies, an in vitro perifusion model was used to compare stimulation of ovarian tissue with either human menopausal gonadotropin (hMG), which is an equal mixture of luteinizing hormone (LH) and follicle stimulating hormone (FSH), or with hMG plus added human FSH. Eight-hour perifusion studies were conducted on either whole, or dissected clusters of follicles from pregnant mare serum gonadotropin (PMSG)-treated rats. In the two groups, similar stimulatory protocols were used, consisting of a ramp stimulation over 60 min with either hMG (0-8 mIU/ml) or hMG plus FSH (0-8 mIU/ml hMG + 0-8 mIU/ml FSH), followed by hourly pulse stimulation with hMG (8-18 mIU/ml) or hMG plus FSH (8-18 mIU/ml hMG + 8-18 mIU/ml FSH), respectively. In the whole ovaries, no differences were detected in progesterone, testosterone, or estradiol secretion. However, in the cluster of follicles, an elevated hFSH/hMG ratio resulted in a significantly higher secretion of progesterone, testosterone and estradiol (n = 8; p < 0.05) than the steroids secreted by follicles perifused with hMG alone. In conclusion, an elevated FSH: LH ratio led to greater steroidogenic responses by the perifused cluster of follicles, but not by the whole ovary.
Animals↗