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At least 595 records · Page 33Linked to original sources
PubMed2000

Immunohistochemical detection of plasminogen activator inhibitor-1 in polycystic ovaries.

Anovulation in women with polycystic ovary syndrome (PCOS) is incompletely understood. The concentration of the glycoprotein plasminogen activator inhibitor-1 (PAI-1) is raised in insulin resistance. This has been described in the granulosa and theca cell layers of the animal but not the human ovary. This study was performed to investigate the location of PAI-1 in the human ovary and investigate whether it may contribute to anovulation in PCOS. PAI-1 was localized immunohistochemically and quantitated using computer image analysis in 17 ovarian follicles from five women with a diagnosis of PCOS and compared with 15 follicles from six normal ovaries. PAI-1 was predominantly found in the granulosa and theca cells in both polycystic and normal ovaries. Image analysis did not reveal a difference in the PAI-1 signal from polycystic compared with normal ovaries. This study shows that PAI-1 plays a role in human ovulation, but its role in PCOS requires further research.

Adolescent↗
PubMed1991

[Hyperplastic processes and endometrial cancer in patients with hormone-producing ovarian tumors].

Status of the endometrium was assessed in 357 patients with hormone-producing tumors of the ovaries of major histological types such as theca cell (161 cases), granulosa cell (123) and mixed theca-granulosa cell tumors (22) as well as androblastoma (23) and Brenner's tumor (28 patients). Hyperplastic lesions of the endometrium, cancer included, were established in 250 (74.8%) patients with feminizing hormone-producing tumors whereas androblastoma patients showed either atrophic or normal endometrium (78.3% cases) and failed to reveal atypical hyperplasia or cancer of that site.

Brenner Tumor↗
PubMed1995

Proliferating cell nuclear antigen marks the initiation of follicular growth in the rat.

Despite expanding knowledge on the kinetic aspects of folliculogenesis, the question of what initiates follicle growth remains unanswered. Efforts to solve this problem have been thwarted by the absence of sensitive markers to identify the onset of follicular growth. In this study, we determined whether increased proliferating cell nuclear antigen (PCNA) correlates with initiation of follicle growth and might therefore be useful for studying early events in this process. Paraffin sections of ovaries from cycling adult rats, prepubertal eCG+hCG-primed rats, and prepubertal control rats were processed for immunocytochemistry by use of a PCNA primary antibody. In primordial follicles, neither granulosa cells nor oocytes stained for PCNA. PCNA immunoreactivity coincided with the earliest sign of follicle growth, appearing in pregranulosa cells of early primary follicles just beginning to grow. In all primary follicles, some granulosa cells were PCNA-positive. PCNA immunoreactivity in oocytes first appeared in primary follicles, preceding oocyte enlargement. In preantral and antral follicles, granulosa cell PCNA staining was uniform throughout the granulosa cell layers. Oocytes were positive for PCNA in both preantral and antral follicles. PCNA expression diminished in atretic follicles. In CL, granulosa cell PCNA expression was also decreased. Theca cell PCNA expression was first evident in the transitional follicle (1-2-layer granulosa cells) and was present in all stages thereafter. The pattern of PCNA expression did not differ among adult cycling, prepubertal eCG+hCG-stimulated, and control rat ovaries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Regulation of expression of ovarian mRNA encoding steroidogenic enzymes and gonadotrophin receptors by FSH and GH in hypogonadotrophic cattle.

A study was conducted to determine the effects of FSH and bovine somatotrophin on the expression of mRNA encoding the gonadotrophin receptors and steroidogenic enzymes in ovarian follicles of cattle rendered hypogonadotrophic by treatment with a GnRH agonist. Hereford x Friesian heifers were allotted into two pretreatment groups: controls (n = 10) and GnRH agonist-treated (n = 20). Ovaries of control cows were removed on day 2 of the first follicular wave after synchronized oestrus. GnRH agonist-treated heifers were given either FSH or no FSH. FSH was infused at 50 microg h(-1) for 48 h. Ovaries in GnRH agonist-treated heifers were removed at the end of exogenous hormone treatment. The control, GnRH agonist and GnRH agonist plus FSH treatment groups were divided further into bovine somatotrophin or no bovine somatotrophin treatments (n = 5 per treatment). Bovine somatotrophin (25 mg day(-1) by s.c. injection) was administered for 3 days. Ovaries were scanned once a day by ultrasonography. Blood samples for hormone measurements were collected three times a day from oestrus until the time of removal of ovaries. Expression of mRNAs for the FSH and LH receptors and cytochrome P450 side-chain cleavage (P450scc), cytochrome P450 17alpha-hydroxylase (P450c17) and cytochrome P450 aromatase (P450arom) enzymes was localized by in situ hybridization and quantified by image analysis. Ovarian follicular growth was arrested at < or = 4.5 mm in diameter in GnRH agonist-treated heifers. There was no effect of bovine somatotrophin on follicular dynamics, gonadotrophin secretion or expression of mRNA for either the gonadotrophin receptors or steroidogenic enzymes. Infusion of FSH to GnRH agonist-treated heifers increased FSH concentrations in serum to the physiological concentrations observed in controls and stimulated growth of follicles to a size similar (5.5-8.0 mm in diameter) to recruited follicles in control cows. FSH induced mRNA expression of P450scc and P450arom in granulosa cells of follicles at a smaller size (< or = 4.5 mm in diameter) than in controls and increased (P < 0.001) expression in larger (> 4.5 mm in diameter) follicles. Expression of mRNAs for P450scc and P450c17 increased (P < 0.001) with increasing follicle size and was higher (P < 0.01) in theca cells of GnRH agonist plus FSH-treated heifers than in the other groups. There were no treatment differences in expression of FSH receptor in granulosa cells or LH receptor in theca cells, but expression of both receptors increased with follicle size. There was no expression of LH receptor in the granulosa cells of cows from any treatment group. In conclusion, FSH treatment in GnRH agonist-treated heifers induced similar changes in follicular growth to those observed during the first follicular wave, but despite similar peak concentrations, prolonged exposure to high FSH induced precocious expression of mRNAs for P450scc and P450arom in granulosa cells from small follicles and markedly upregulated expression of these enzymes in granulosa cells from recruited follicles. The results of this study demonstrate the key role that FSH plays in the induction of follicular growth and differentiation.

Animals↗
PubMedDate not supplied

[Virilizing granulosa-cell tumors of the ovaries].

On the basis of the results of morphological and histochemical study of two malignant granulosa cell tumours removed in women with the virile syndrome the author came to the conclusion that theca-tissue was a necessary structural component of such tumours. Theca cell component can be expressed to a different extent, but its cells, in contrary to the cells of the prevailing ganulosa cell component of such tumours, possessed a high enzymatic activity providing the processes of the steroid hormone biosynthesis, and contained lipids intimately connected with these processes. These data permit to regard the theca cell component of malignant granulosa cell tumours as the main source of hormones produced by such tumours.

Aged↗
PubMed2003

Heme oxygenase in the rat ovary: immunohistochemical localization and possible role in steroidogenesis.

The objectives of this study were to determine if heme oxygenase (HO), which catalyzes the degradation of heme and the formation of carbon monoxide (CO), is localized in the rat ovary and, if so, to determine if hemin (a substrate for HO) or chromium mesoporphyrin (CrMP, an inhibitor of HO), alter basal or gonadotropin-induced steroidogenesis. The hypothesis was that CO produced endogenously by HO suppresses steroid hormone production by the ovary similar to the action of nitric oxide. For the histological localization of HO, sections of ovaries obtained from mature Holtzman Sprague-Dawley rats were immunostained for two of the HO isoforms, HO-1 and HO-2. Theca cells and granulosa cells of follicles and luteal cells stained for HO-1, whereas the ovarian stroma showed a low intensity of staining. Theca, granulosa cells, and corpora lutea as well as the ovarian stroma exhibited HO-2 staining. HO-2 immunostaining appeared more intense for theca cells than granulosa cells. In the study of steroidogenesis, three daily injections of hemin stimulated basal- and gonadotropin-induced androstenedione and estradiol secretion from ovaries of pregnant mare serum gonadotropin-treated immature rats in vitro, but had no effect on progesterone production. A similar treatment with CrMP suppressed basal- and gonadotropin-induced secretion of progesterone and androstenedione, but had no effect on estradiol production. These data, taken together, show the existence of HO in the rat ovary and suggest a possible stimulatory role of endogenous CO in the production of ovarian steroids.

Animals↗
PubMed2003

Pregnancy after administration of high dose recombinant human LH alone to support final stages of follicular maturation in a woman with long-standing hypogonadotrophic hypogonadism.

Traditionally, the roles of LH in folliculogenesis have been considered to be limited to stimulating theca cells androgen production, triggering ovulation and supporting the corpus luteum. However, in the late stages of follicle development, granulosa cells become receptive to LH stimulation and LH becomes capable of exerting its actions on both theca cells and granulosa cells. Thus, it has been postulated that once an appropriate (i.e. LH-responsive) stage of follicular development has been achieved in response to treatment with FSH, there are theoretical grounds for reducing or completely withdrawing FSH and maintaining tonic stimulation of the dominant follicle with exogenous LH. This hypothesis was tested in a woman with long-standing hypogonadotrophic hypogonadism, which is the best and only true model to investigate correctly any LH hypothesis. Ovulation induction treatment was carried out with daily s.c. injections of 150 IU recombinant human FSH (rhFSH) (increased to 225 IU daily on stimulation day 15) and 375 IU recombinant human LH (rhLH). When a 14-mm follicle was identified on stimulation day 26, rhFSH was discontinued and from treatment days 26 to 29 the patient was given only rhLH at the above-mentioned dose of 375 IU/day. On treatment day 30, the single dominant follicle measured 22 mm in diameter and oestradiol serum concentration was 148 pg/ml. Thus, an injection of 10,000 IU i.m. human chorionic gonadotrophin was given and sexual intercourse was advised. The patient conceived and a viable singleton intrauterine pregnancy was obtained.

Adult↗
PubMed1994

Induction of prostaglandin endoperoxide synthase-2 by human chorionic gonadotropin in bovine preovulatory follicles in vivo.

Gonadotropins have recently been shown to induce prostaglandin endoperoxide synthase-2 (PGHS-2) in rat preovulatory follicles before ovulation, but hormonal induction of this enzyme has not yet been reported in preovulatory follicles of any other species. To determine whether the selective induction of PGHS-2 by the ovulatory gonadotropin surge is a molecular process that has been conserved in other mammalian species with different reproductive cycles, the regulation of PGHS isoforms was studied in bovine preovulatory follicles isolated 0, 6, 12, 18, 20, 22, 24, and 26 h after an ovulatory dose of hCG. Each follicle was dissected into three preparations: the intact follicle wall (i.e. theca interna with attached granulosa cells), theca interna, and isolated granulosa cells. Solubilized cell extracts were obtained from each preparation and analyzed by Western blots, using polyclonal antibodies that selectively recognize PGHS-2 and PGHS-1 isoforms. RNA extracts were prepared and analyzed by Northern blots, using a mouse PGHS-2 complementary DNA. The results indicated that the expression of PGHS-2 messenger RNA (mRNA) and protein, but not that of PGHS-1, was regulated by hCG in bovine preovulatory follicles before ovulation. Levels of PGHS-2 protein (mol wt, 74,000) in the follicle wall were undetectable at 0, 6, and 12 h, but increased dramatically after 18 h to reach maximal levels 24 h post-hCG treatment. Northern blots revealed a similar temporal induction of PGHS-2 mRNA (4.0 kilobases). Analyses of isolated preparations of theca interna and granulosa cells clearly showed that PGHS-2 was expressed exclusively in granulosa cells and not in theca interna. Significant increases in follicular fluid concentrations of prostaglandins E2 and F were associated with the induction of follicular PGHS-2 protein and mRNA. Thus, this study establishes that the induction by gonadotropin of PGHS-2 in granulosa cells before ovulation appears to be a conserved mechanism by which the synthesis of prostaglandins necessary for the ovulation process is regulated in different species. However, the striking difference between the time course of PGHS-2 induction previously reported in rat follicles (4 h post-hCG treatment) and that observed in bovine follicles (18 h post-hCG treatment) suggests that the control of PGHS-2 expression could be one of the determinants involved in dictating the species-specific progression (length) of the ovulation process.

Animals↗
PubMed2005

Cyclic changes in messenger RNAs encoding inhibin/activin subunits in the ovary of the golden hamster (Mesocricetus auratus).

To elucidate changing patterns of inhibin/activin subunit mRNAs in the ovary of the golden hamster (Mesocricetus auratus) during the oestrous cycle, inhibin/activin subunit cDNAs of this species were cloned and ribonuclease protection assay and in situ hybridization were carried out. Inhibin alpha-subunit mRNA was localized in granulosa cells of primary, secondary, tertiary and atretic follicles throughout the 4-day oestrous cycle. It was also expressed in luteal cells on days 1 (oestrus), 2 (metoestrus) and 3 (dioestrus). betaA-subunit mRNA was localized in granulosa cells of large secondary (>200 microm) and tertiary follicles throughout the oestrous cycle. betaB-subunit mRNA was confined to granulosa cells of large secondary and tertiary follicles. Both alpha- and betaA-subunit mRNAs were also found in ovarian interstitial cells and theca interna cells of tertiary and atretic follicles in the evening of day 4 (pro-oestrus). A striking increase in betaA-subunit mRNA levels was also observed during the preovulatory period. The expression pattern of betaA-subunit mRNA during the preovulatory period is unique and not found in other species. An i.v. injection of anti-luteinizing hormone-releasing hormone (LHRH) serum before the LH surge abolished the expression of alpha- and betaA-subunit mRNAs in ovarian interstitial cells and theca interna cells. The treatment also abolished the preovulatory increase in betaA-subunit mRNA. Furthermore, administration of human chorionic gonadotrophin (hCG), which followed the injection of anti-LHRH serum, restored the expression patterns of alpha- and betaA-subunit mRNAs. The present study revealed that the golden hamster showed a unique expression pattern of betaA-subunit mRNA in response to the LH surge.

Activins↗
PubMed1981

[Malignancy of hormonally active ovarian tumors].

401 cases of hormone-producing tumors of the ovary were studied (190 theca-cell, 169--granulose cell, 25--mixed thecagranulosa cell and 17--virilising tumors). Histological diagnosis, clinical stage and end results of their treatment were compared. Theca-granulosa cell tumor is considered to be the most malignant form of these neoplasms. Pure theca-cell tumor proved to be benign in most cases. Of special interest is a high percentage of patients being cured at stage 1 (FIGO classification) of neoplastic process, that stands, in the authors' opinion, in close relationship with comparatively good results obtained in these patients.

Adenoma↗
PubMed2026

Ovarian expression and function of neuropeptide systems in teleosts and anurans.

The hypothalamic-pituitary-gonadal axis regulates reproduction, sexual maturation, and spawning behaviours. Its evolutionary origins trace back to primitive jawless fish and has been well characterized in teleosts. Recent advances in multi-species genome sequencing, annotation, and experimental approaches for identifying and characterizing key regulators have advanced understanding of neuroendocrine regulation in teleost reproduction, reshaping existing models. Early studies in amphibians established that steroids are critical regulators of final oocyte maturation. Subsequent work in anurans revealed complex interactions among theca cells, follicular cells, and oocytes, supporting a three-cell model in which oocytes contribute to their own steroidogenic environment, challenging the traditional two-cell view of ovarian steroidogenesis. In teleosts, however, direct evidence that oocytes support steroid precursor delivery to theca and follicular cells is limited, and whether a comparable three-cell model applies remains an open hypothesis. Across both taxa, the roles of locally produced neuropeptides in coordinating interactions among theca cells, follicular cells, and oocytes remain largely uncharacterized. Here, we provide a short review of the localization and potential autocrine/paracrine functions of neuropeptides in teleost and amphibian ovaries and discuss existing knowledge gaps. We identify opportunities to leverage detailed localization studies that map neuropeptides to specific ovarian cell types and developmental stages, and discuss how integrating traditional and emerging experimental approaches can advance comparative studies in ovarian endocrinology. This work will improve our understanding of reproductive regulation in fishes and frogs, with applications in captive breeding, aquaculture, and endocrine disruption research.

Autocrine↗
PubMed1989

Ovarian nerve extracts influence androgen production by cultured ovarian thecal cells.

There is growing evidence that ovarian steroidogenesis is controlled not only by pituitary gonadotropins but also by ovarian nerves. Nerves reach the ovary via the plexus nerve and via the superior ovarian nerve (SON), which runs in the suspensory ligament, and innervate theca cells of all sizes of follicles. To investigate the role of ovarian nerves in steroidogenesis we have examined the effects of adding an extract of SON from adult rats on androgen production by cultured porcine theca cells. Addition of SON extract to cultured theca interna from 3 to 6 mm diameter follicles of prepubertal gilts significantly inhibited (p less than 0.05) LH-stimulated androstenedione production in a dose-dependent manner; significant inhibition (10.8%) occurred with the addition of the extract of 2 mg of SON/ml culture medium, and near maximal inhibition (83%) resulted when the SON extract was increased to 60 mg SON/ml. Extracts of sciatic nerves, used as non-ovarian nerve controls, failed to inhibit, and in fact significantly increased (p less than 0.05) androstenedione production over the same concentration range of neural tissue extract. The inhibitory effect of the SON extract was unaffected by chymotrypsin digestion or by the presence of the beta-adrenergic antagonist propranolol (10(-6) M), but was removed by charcoal treatment. These results suggest that the nervous system has the potential for modulation of follicular steroid biosynthesis via direct innervation of the ovaries, in addition to the well-established indirect mechanism of neural control exerted via the hypothalamic-pituitary system.

Adipose Tissue↗
PubMed2004

Expression of progesterone receptors A and B in the mouse ovary during the estrous cycle.

Progesterone plays a central role in the regulation of ovarian function. The progesterone receptor (PR) has been shown to be essential for ovulation because mice lacking PR fail to ovulate and are infertile. PR is expressed as two isoforms, PRA and PRB, which have been shown to have different functional activities. In this study, we investigated the cellular distribution of PRA and PRB in the ovaries and oviducts of cycling mice using immunohistochemistry with isoform-specific monoclonal antibodies. In the ovary, on the evening of proestrus before ovulation, both the granulosa and theca cells of the preovulatory follicles expressed both PR isoforms. PRA and PRB staining was also observed in the theca cells of preantral and antral follicles, whereas only PRB was observed in the granulosa cells of primary, preantral, and antral follicles and in the corpus luteum. In the oviduct, PRA was the predominant isoform observed, expressed in both the epithelial and stromal cells, whereas PRB was only detected in the epithelial cells. The differences in PRA and PRB localization in the ovary and oviduct may reflect diverse functions for PRA and PRB in reproductive tissues and may have important implications in understanding the mechanisms of progesterone action.

Animals↗
PubMed1998

LH receptor mRNA and cytochrome P450 side-chain cleavage expression in bovine theca and granulosa cells luteinized by LH or forskolin.

This study was undertaken to characterize the cDNA sequence encoding bovine LH receptor (LHR), and study the effect of different luteinization protocols on the steroidogenic capacity and LHR mRNA in bovine luteal cells. The bovine LHR cDNA sequence reported here showed high sequence identity with that of other species. Several mRNA splice variants were expressed in bovine corpus luteum (CL). Reverse transcription-polymerase chain reaction conducted with primers spanning exons 2-11 revealed, in addition to the full-length sequence, a shorter fragment homologous to splice variant B reported in porcine and ovine LHR cDNA sequences. Granulosa and theca cells derived from bovine preovulatory follicles were cultured with either forskolin (10 microM, for 8 d culture-Protocol 1) or LH (100 ng/ml, for 12 hr followed by a 7.5-d culture with 2 ng/ml-Protocol 2). LHR mRNA was not detected in luteal granulosa cells (LG); in contrast, luteal theca cells (LT) contained LHR mRNA at similar levels when cultured under Protocol 1 or 2. cAMP responses to a short challenge with LH were in good agreement with LHR mRNA levels. Cytochrome P450 side-chain-cleavage (P450scc) contents were lower in luteal cells cultured with LH as compared with cells cultured with forskolin; however, the difference between the two luteinization protocols was much larger in LT (P < 0.05) than in LG. This study suggests that a) LHR mRNA is mainly present in the theca-derived luteal cell and b) LHR mRNA and cytochrome P450scc expression in each of the luteal cell types seems to be under different control.

Amino Acid Sequence↗
PubMedDate not supplied

Estrogenic and antiestrogenic effect of in vitro treatment of follicular cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

OBJECTIVE: Two types of follicular cells from preovulatory ovary were cultured in vitro separately and in co-culture to test difference in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) action on particular cell types. METHODS: The accumulation of TCDD in follicular wall was analysed using coupled capillary gas chromatography mass spectrometry. Whole preovulatory follicles were isolated from ovary and incubated with prolonged exposure to 0.1 nM TCDD or single exposure to 10 nM TCDD for four days. In the second part of experiments direct effects of TCDD on steroidogenesis were investigated in porcine theca cells (Tc) and granulosa cells (Gc) cultured alone and in co-culture (GT). The media were collected after four days for steroid analysis. RESULTS: 59.3% and 81.2% of TCDD added to the culture medium was accumulated after 0.1 and 10 nM, respectively. TCDD in a dose-dependent manner increased estradiol secretion with concomitant progesterone secretion by theca interna cells. On the other hand decrease of both progesterone and estradiol secretion by granulosa cells cultured alone and in co-culture with theca cells was noted. CONCLUSION: Different cell-specific estrogenic or antiestrogenic effect of TCDD were found in ovarian follicles.

Animals↗
PubMed2006

AMP-activated protein kinase activation modulates progesterone secretion in granulosa cells from hen preovulatory follicles.

AMP-activated protein kinase (AMPK) is a fuel sensor in glucose, lipid, and cholesterol metabolism. Using RT-PCR and Western blot, AMPK subunits mRNAs (alpha1/2, beta1/2, and gamma1/2) and proteins (alpha1/2 and beta1/2) can be found in the hen preovulatory follicles and precisely in both granulosa and theca cells. These preovulatory follicles are organized in a hierarchy according to their size (F5/6 to F1). The smallest number (F1) corresponds to the largest size and the latest mature stage. Phosphorylation of AMPKalpha on Thr172 and of acetyl-CoA carboxylase on Ser79 are higher in F4 and F3 than in F1 granulosa cells. However, they are not affected in F4-F1 theca cells. Treatment with 1 mM 5-amino-imidazole-4-carboxyamide-1-beta-D-ribofuranoside (AICAR), an activator of AMPK, dose dependently increased phosphorylation of AMPKalpha on Thr172 in primary F3/4 and F1 granulosa cells. In the absence of FSH, AICAR treatment increased progesterone, P450 side chain cleavage and steroidogenic acute regulatory (StAR) production in both F3/4 and F1 granulosa cells. However, in the presence of FSH, AICAR treatment for 36 h increased progesterone secretion, StAR protein levels and reduced extracellular signal-regulated kinase (ERK)1/2 phosphorylation in F3/4 granulosa cells. Opposite data were observed in F1 granulosa cells. Adenovirus-mediated expression of dominant-negative AMPK totally restored the effects of AICAR on FSH-induced progesterone secretion, StAR protein production, and ERK1/2 phosphorylation in F3/4 and F1 granulosa cells. Using a specific inhibitor of ERK1/2 (U0126), we also showed that this kinase is a negative regulator of the FSH-induced progesterone secretion in F3/4 and F1 granulosa cells, suggesting that AICAR-mediated AMPK activation modifies FSH-induced progesterone secretion differently through the ERK1/2 signaling pathway in hen F3/4 and F1 granulosa cells.

AMP-Activated Protein Kinases↗
PubMed1990

Steroidogenesis in porcine follicle cells cultured in serum-free media.

The purpose of this study was to determine the steroid production of cultured porcine follicle cells grown in serum-free media. Theca cells (TC) and granulosa cells (GC) from large porcine follicles (greater than 8 mm) were dispersed and plated as monolayer cultures in serum-free media. Media were removed from the cultures at 3, 6, 12, 24, 48, 72, 96, and 120 h and assayed for estradiol, progesterone, testosterone and androstenedione. Both GC and TC were capable of producing progesterone, androgens and estradiol in serum-free media. GC were responsive to human chorionic gonadotropin and follicle-stimulating hormone while TC were only responsive to human chorionic gonadotropin. Growth factors, particularly insulin, appeared to enhance ovarian cells' steroidogenesis.

Animals↗
PubMed1995

Virilization associated with choriocarcinoma.

We demonstrate here two autopsy-proven cases of virilization associated with choriocarcinoma. The first patient was a 27-year-old woman with a 7-year history of metastatic choriocarcinoma who presented with left hemiparesis and virilization. Serum testosterone concentration was 18 nmol/l, free testosterone 471 pmol/l, dehydroepiandrosterone sulphate (DHEA-sulphate) 1.7 mumol/l, sex hormone binding globulin 12.3 nmol/l, estradiol (E2) 1,843 pmol/l, and hCG 1.6 x 10(5) IU/l. The second patient was a 21-year-old virilized woman with metastatic choriocarcinoma who presented in semicomatose state. Limited endocrine investigation revealed serum testosterone 27 nmol/l and hCG 2.7 x 10(5) IU/l. Both patients died despite chemotherapy and radiation therapy. Autopsy findings revealed choriocarcinoma with brain and multiple organ metastasis in both. Pathology of the ovaries of both patients demonstrated hyperplasia of luteinized theca cells and lutein cells. We postulate that an association of virilization and choriocarcinoma resulted from long-standing stimulation of ovary by hCG causing theca cell hyperplasia with subsequent hypertestosteronemia and virilization.

Adult↗