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PubMed2005

Diagnosis and surgical removal of a granulosa-theca cell tumor in a mare.

An 8-year-old mare showed stallion-like behavior and aggressiveness. A granulosa-theca cell tumor was tentatively diagnosed based on history, transrectal palpation, and ultrasonography, and surgically removed. Serological levels of testosterone and inhibin were elevated. Histopathological examination confirmed the diagnosis. The mare recovered and by day 45 could be turned out with other horses.

Animals↗
PubMed2000

In vivo treatment with GDF-9 stimulates primordial and primary follicle progression and theca cell marker CYP17 in ovaries of immature rats.

Growth differentiation factor (GDF)-9 is a cystine knot-containing hormone of the transforming growth factor-beta superfamily produced by the oocyte. In GDF-9 null mice, follicle development is arrested at the primary stage and GDF-9 treatment in vitro enhances preantral follicle growth. Immature female rats were treated with recombinant GDF-9 for 7 or 10 days. At 10 days, treatment with GDF-9 augmented ovarian weights, concomitant with an increase in the number of primary and small preantral follicles by 30 and 60%, respectively. Furthermore, the number of primordial follicles was decreased by 29%, but the number of large preantral follicles was not affected. In contrast, treatment with FSH increased the number of small and large preantral follicles by 36 and 177% but did not influence the number of primary and primordial follicles. Immunoblot analysis showed an increase of CYP17, a theca cell marker, in the ovarian homogenate after treatment with GDF-9 but not FSH. The present results indicate that in vivo treatment with GDF-9 enhances the progression of primordial and primary follicles into small preantral follicles. Thus, GDF-9 treatment could provide an alternative approach to stimulate early follicle development in addition to the widely used FSH that acts mainly on the development of more advanced follicles.

Animals↗
PubMed2005

Selective theca cell dysfunction in autoimmune oophoritis results in multifollicular development, decreased estradiol, and elevated inhibin B levels.

We describe the clinical course of three women with presumptive autoimmune oophoritis who developed multiple follicles but very low to undetectable estradiol levels. Multiple follicles developed spontaneously in all subjects and during pulsatile GnRH treatment for ovulation induction in subject 1. The development of multiple dominant follicles was accompanied by LH levels in the postmenopausal range and FSH levels at the upper limit for premenopausal women. Serum inhibin B levels were elevated appropriately in the setting of multifollicular development, but estradiol levels remained low. Measurement of estradiol precursors demonstrated androstenedione and estrone levels below the 95th percentile in normal women. Adrenal cortical antibodies, and antibodies to 21-hydroxylase and P450 side chain cleavage enzymes were identified in all subjects. All subjects met the criteria for premature ovarian failure during follow-up. Subject 1 later developed adrenal failure, whereas subject 3 had adrenal failure at the time of the study. These subjects elucidate the hormonal pattern in autoimmune oophoritis, before the full criteria for premature ovarian failure are met. The elevated inhibin A and B levels, which accompany the development of multiple small and dominant follicles in these women, suppress FSH relative to LH levels, virtually independent of estradiol. These data provide further evidence for an important role of inhibin B and inhibin A in the negative feedback control of FSH. In addition, the normal inhibin A and inhibin B production in the absence of estradiol precursors and estradiol provide insight into the selective dysfunction of the theca cells in autoimmune oophoritis.

Adolescent↗
PubMed1999

Dimeric inhibin concentrations in mares with granulosa-theca cell tumors.

OBJECTIVE: To determine whether concentrations of dimeric inhibin (CaCA) are greater in plasma and tumor fluid from mares with granulosa-theca cell tumors (GTCT), compared with concentrations in plasma and equine follicular fluid (eFF) from control mares. ANIMALS: 6 mares with GTCT and 12 clinically normal mares. PROCEDURE: The alphabetaA immunoradiometric assay used 2 antibodies, one against each subunit of inhibin (alpha and betaA subunits). Tumor tissue, tumor fluid, and a single blood sample were collected at the time of surgical removal of the GTCT. A single blood sample was collected from 7 control mares during various stages of the estrous cycle. Five other control mares were ovariectomized when their ovaries contained growing follicles of 25 to 35 mm in diameter. A blood sample and eFF from the largest follicle were collected at the time of ovariectomy. RESULTS: Mares with GTCT had significantly greater plasma concentrations of betabetaA (mean +/- SEM, 0.86 +/- 0.53 ng of recombinant human-alphabetaA/ml), compared with control mares (0.14+/-0.02 ng/ml). Concentrations of alphabetaA in tumor fluid and eFF were similar. Concentrations of alphabetaA were significantly lower after ovariectomy. CONCLUSIONS AND CLINICAL RELEVANCE: Dimeric inhibin concentration was higher in plasma from mares with GTCT than in plasma from control mares. Increased granulosa cell mass and loss of mechanisms regulating alphabetaA release in mares with GTCT likely accounted for the increase in plasma concentrations. Measurement of alphabetaA concentrations may be useful for identifying mares with GTCT.

Animals↗
PubMed1996

Transforming growth factor beta expression in the porcine ovary: evidence that theca cells are the major secretory source during antral follicle development.

The transforming growth factors beta (TGF beta) have been implicated as important intrafollicular regulators of follicle development in the mammalian ovary. Recent studies in this laboratory have suggested that, when cultured, both porcine theca and granulosa cells secrete TGF beta, primarily TGF beta 1 (May et al., Endocrine 2:1045-1054, 1994). In this report, evidence is presented that during follicle development in vivo, theca but not granulosa cells are the source of follicular TGF beta. Although both theca and granulosa cells secreted TGF beta when attached to culture dishes, only theca cells secreted detectable levels of TGF beta when cells were cultured in serum-free medium without attachment. Granulosa cells secreted little if any TGF beta. This difference in TGF beta secretion was not found to be due to differences in preparation of the two cell types (i.e., mechanical versus enzymatic preparation). These results suggested that theca cells may be the source of TGF beta in the follicle. To ascertain whether TGF beta is actually secreted by follicles, intact hemi-follicle linings consisting of both theca and granulosa cells were cultured in moderate-term, organ explant culture. Hemi-follicle linings secreted TGF beta at a near linear rate for at least 4 days (approximately 300 pg/follicle/day for 6-8-mm-diameter follicles). The level of TGF beta secretion was directly related to the size of the follicle (p < 0.01). Immunoneutralization studies using TGF beta subtype-specific antibodies indicated that the major form of TGF beta secreted by porcine hemi-follicle linings was TGF beta 1. To further investigate the source of TGF beta during follicle development, a combination of molecular biology procedures was employed. Using 243-bp antisense and sense cRNA probes generated from a simian TGF beta 1 cDNA, we performed in situ hybridization on sections of whole porcine ovaries containing antral follicles. Expression of TGF beta 1 mRNA was localized to both theca and granulosa cells with no expression found in the stroma, suggesting that both cell types transcribe TGF beta 1. TGF beta 1 expression was evaluated additionally by reverse transcriptase polymerase chain reaction (RT-PCR) and Northern blot analysis. Oligonucleotide primers were generated from the porcine TGF beta 1 cDNA sequence for RT-PCR, and the PCR product (287-bp sequence) was amplified and used for Northern analysis. RT-PCR of total RNA isolated from theca and granulosa cells indicated that both cell types expressed TGF beta 1 mRNA. This finding was confirmed via Northern blot analysis, which further indicated the presence of two TGF beta 1 mRNAs of 2.5 and 3.5 kb, consistent with previous reports of alternate splicing of the porcine TGF beta 1 gene. These data indicate that both cell types express TGF beta 1 mRNA. To further evaluate TGF beta 1 expression, we attempted to isolate TGF beta 1 protein from freshly collected theca and granulosa cells by partial purification and immunoprecipitation. Interestingly, the growth factor could be extracted only from theca cells, not from granulosa cells, despite the presence of mRNA in both cell types. Taken together, these data suggest that whereas both theca and granulosa cells produce the TGF beta 1 gene product, only theca cells translate and secrete the actual growth factor. Thus, it is likely that the theca is the source of the growth factor during follicle development.

Animals↗
PubMed1985

Granulosa-theca cell tumor in a one-year-old infant.

A case is presented of a 12-month-old female infant, with sexual precocity due to a Granulosa-Theca cell tumor which presented with vaginal bleeding, breast development and public hair growth. The 17 beta-estradiol levels prior to operation were 300 pg/ml. Levels of gonadotropins were undetectable. Postoperative estradiol levels were measured and found to be 10 pg/ml. This tumor is very rate in infants, and there have been only four previously reported cases in children under 2 years of age.

Estradiol↗
PubMed1978

Origin of estrogen in isosexual precocious pseudopuberty due to a granulosa-theca cell tumor.

The purpose of the present study was to quantify the rates of production and to define the mechanism(s) or origin of sex steroid hormones in a 3 1/2-year-old girl with isosexual precocious pseudopuberty caused by a granulosa-theca cell tumor of the ovary. The results suggest that the hyperestrogenism occurs principally due to the secretion of estradiol-17beta synthesized de novo by the tumor, but that the tumor in vivo was also capable of aromatizing C19 plasma precursor hormones to estrogen.

Child, Preschool↗
PubMed2003

Malignant granulosa-theca cell tumor in a two-year-old Miniature Horse.

A 2-year-old female Miniature Horse that presented with a history of progressive weight loss, depression, and diarrhea was diagnosed at necropsy with a highly malignant abdominal neoplasm involving the left ovary, kidneys, adrenal glands, intestines, and various abdominal and thoracic lymph nodes. Microscopic examination of these masses revealed large pleomorphic cells that stained positive for vimentin and inhibin and negative for epithelial membrane antigen and placental alkaline phosphatase. Ultrastructural examination of the cells revealed a high nucleocytoplasmic ratio and indented euchromatic nuclei with large nucleoli. Based on the gross, microscopic, immunohistochemical, and ultrastructural features, the neoplasm was identified as a malignant granulosa-theca cell tumor, a rare neoplasm in young horses.

Animals↗
PubMed1997

Ovarian torsion associated with granulosa-theca cell tumor in a mare.

A 12-year-old Morgan mare was examined because of stallion-like behavior of 45 days' duration. Palpation per rectum and transrectal ultrasonographic examination revealed a large left ovary with multiple cystic areas and crepitus. A granulosa-theca cell tumor was suspected. During hospitalization for further evaluation of the affected ovary, the mare developed signs of abdominal pain. Exploratory surgery revealed a large left ovary, which was black with a necrotic and friable surface, and a 720 degrees clock-wise torsion of the ovarian pedicle. Torsion was corrected, and oophorectomy was performed. The mare recovered satisfactorily from surgery. Histologic diagnosis was granulosatheca cell tumor with marked diffuse necrosis. To our knowledge, torsion of the ovarian pedicle has not been reported in the veterinary literature. However, it is not uncommon in women. Ovarian torsion seems to develop in association with neoplasia, cysts, and ovarian hyperstimulation syndrome. Ovarian torsion should be considered as a differential diagnosis for mares with a known ovarian pathologic change such as neoplasia or abscess if signs of abdominal pain are evident.

Animals↗
PubMed1992

Differential expression of aminopeptidase-N on human ovarian granulosa and theca cells.

The expression of aminopeptidase-N and neutral endopeptidase in human ovarian tissue was examined using specific monoclonal antibodies for each of these peptidases and histochemical staining for enzyme activity. Aminopeptidase-N is a membrane-bound metalloprotease catalyzing the removal of N-terminal amino acids from peptides and was detected by immunofluorescence staining on theca interna cells in secondary follicles and on luteinized thecal cells in preovulatory follicles and corpora lutea. However, aminopeptidase-N was not detected on granulosa cells. Peptidase activity was also detected by histochemical staining on theca interna cells and luteinized thecal cells. Luteinized granulosa cells showed peptidase activity, despite the lack of aminopeptidase-N. Neutral endopeptidase was not detected in ovarian granulosa and thecal cells. These observations indicate that aminopeptidase-N can be a useful surface marker for thecal cells.

Adult↗