Expression and characterization of androgen receptor coregulators, SRC-2 and HBO1, during human testis ontogenesis and in androgen signaling deficient patients.

Androgen receptor (AR) is essential for testicular physiology and spermatogenesis. SRC-2 and HBO1 are two AR coregulators yet their expression and roles in human testis are unknown. For the first time, we studied by immunohistochemistry and RT-PCR, the expression and distribution of these two coregulators during human testicular ontogenesis, in patients with altered AR signaling (Androgen insensitivity syndrome, AIS) and evaluated the functional impact of SRC-2 and HBO1 on AR signaling in a Sertoli cell context. SRC-2 was present in Sertoli cells at all developmental stages. HBO1 was barely or focally detected in the fetal testis yet its expression, in Sertoli and germ cells, drastically increased postnatally from early infancy to adulthood. In transient co-transfection studies we showed that SRC-2 induced, while HBO1 inhibited AR-mediated transactivation of reporter constructs in murine Sertoli SMAT1 cells. HBO1, but not SRC-2, expression was reduced in testes of patients with AIS compared to normal testes.

Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure.

OBJECTIVE: Premature ovarian failure (POF) encompasses a heterogeneous spectrum of conditions, with phenotypic variability among patients. The etiology of POF remains unknown in most cases. We performed a global phenotyping of POF women with the aim of better orienting attempts at an etiological diagnosis. DESIGN AND METHODS: We performed a mixed retrospective and prospective study of clinical, biological, histological, morphological, and genetic data relating to 357 consecutive POF patients between 1997 and 2008. The study was conducted at a reproductive endocrinology referral center. RESULTS: Seventy-six percent of the patients presented with normal puberty and secondary amenorrhea. Family history was present in 14% of the patients, clinical and/or biological autoimmunity in 14.3%. Fifty-six women had a fluctuating form of POF. The presence of follicles was suggested at ultrasonography in 50% of the patients, and observed in 29% at histology; the negative predictive value of the presence of follicles at ultrasonography was 77%. Bone mineral density alterations were found in 58% of the women. Eight patients had X chromosomal abnormalities other than Turner's syndrome, eight other patients evidenced FMR1 pre-mutation. Two other patients had autoimmune polyendocrine syndrome type 2 and 1. CONCLUSION: A genetic cause of POF was identified in 25 patients, i.e. 7% of the whole cohort. POF etiology remains most often undiscovered. Novel strategies of POF phenotyping are in such content mandatory to improve the rate of POF patients for whom etiology is identified.

Primary amenorrhea revealing an occult progesterone-secreting ovarian tumor.

OBJECTIVE: To describe a patient with primary amenorrhea revealing an occult progesterone-secreting ovarian tumor. DESIGN: Case report. SETTING: University medical center. PATIENT(S): A 20-year-old woman with primary amenorrhea. INTERVENTION(S): Investigations to identify the source of progesterone secretion. MAIN OUTCOME MEASURE(S): Discovery of an occult progesterone-secreting ovarian tumor. RESULT(S): Initial ovarian ultrasonography did not show any abnormal mass. Catheterization of ovarian veins suggested a right ovarian source of progesterone. After long-term follow-up, a right ovarian tumor became apparent and was surgically removed. After surgery, progesterone levels decreased and normal ovulatory cycles resumed. Pathologic and immunohistochemical analysis showed a Leydig cell tumor expressing cytochrome P450 side-chain cleavage and 3ss-hydroxysteroïd dehydrogenase enzymes, which are involved in progesterone biosynthesis, whereas P45017alpha-hydroxylase was not expressed, explaining the absence of hyperandrogenemia. Before surgery, two LH pulses were detected during a 6-hour study period and a lack of ovarian response to pulsatile GnRH administration. CONCLUSION: This is the first case of isolated progesterone secretion by an occult ovarian Leydig cell tumor and a novel etiology of primary amenorrhea. The results also suggest that sustained progesterone can exert an inhibitory effect on gonadotropin secretion at both hypothalamic and pituitary levels.

Unusual presentation of Bartholin's gland duct cysts: anterior expansions.

The medical records of 32 patients who underwent surgery for a vulvar mucinous cyst located between the urethral meatus and the fourchette were reviewed. Nineteen (59%) patients had been referred to our centre because of cyst recurrence after incision or excision. The majority of the cysts were lined by a single layer of tall columnar cells with zones of squamous metaplasia. Subacute or chronic bartholinitis was demonstrated in 94% of the cases demonstrating that these cysts were anterior expansions of Bartholin's gland duct cysts. No ipsilateral recurrence was observed after cyst and gland excision.

Frozen section examination of the endocervical margin of cervical conization specimens.

OBJECTIVE: We conducted this retrospective study to determine accuracy of frozen section examination of endocervical margin during cold knife conization. METHODS: Between June 1993 and June 2001, 310 consecutive patients underwent cervical conization for squamous intraepithelial lesion or stage IA1 cervical cancer. Before 1997, the surgical specimens of 149 patients were processed following a standard pathological procedure (historical group). After 1997, a frozen section of the upper endocervical margin was processed during surgery for 161 patients. If the upper endocervical margin was involved with intraepithelial neoplasia, the surgeon performed a second resection if possible. Results of the frozen section examination were compared with the final diagnoses to determine sensitivity, specificity, and positive and negative predictive values. The usefulness of this procedure was evaluated by comparison of positive margin status rate with the one of the historical control group. RESULTS: For the diagnosis of intraepithelial neoplasia involving the endocervical margin, the sensitivity, specificity, and positive and negative predictive values of frozen section were 91%, 100%, 100%, and 98%, respectively. Eleven patients had definitive positive endocervical margin in the frozen section group (three false negatives, six patients without additional resection, and two patients with intraepithelial neoplasia involving the upper margin of the additional resection) and 17 patients in the historical group (P =.16). CONCLUSION: Frozen section examination of the endocervical margin of cervical specimen obtained during cold knife conization is highly accurate. Its clinical relevance has to be demonstrated in a multicenter study.