SECRETION OF C19-STEROIDS AND OESTROGENS IN THE POLYCYSTIC OVARY SYNDROME. OVARIAN STUDIES IN VIVO AND IN VITRO (INCLUDING STUDIES IN VITRO ON A COINCIDENTAL GRANULOSA CELL TUMOUR)

1968 ◽  
Vol 42 (2) ◽  
pp. 229-243 ◽  
Author(s):  
S. L. JEFFCOATE ◽  
R. V. BROOKS ◽  
D. R. LONDON ◽  
F. T. G. PRUNTY ◽  
P. RHODES

SUMMARY Ovarian metabolism of C19-steroids and oestrogens has been assessed at ovarian wedge resection in 22 patients with polycystic ovaries. There were marked variations between different patients. High concentrations of androstenedione were found in ovarian vein plasma in some patients, and always after stimulation with human pituitary follicle-stimulating hormone (HP-FSH) in vivo. Its contribution to the daily production of testosterone has been considered. No measurable amounts of testosterone or dehydroepiandrosterone were found. Oestradiol concentration was sometimes normal or above. Large amounts of androstenedione were generally isolated from cyst fluid. Occasionally testosterone was found and also epitestosterone after FSH. That concentrations of oestrogens in cyst fluid are low was confirmed, but sometimes higher levels were found after FSH. Slices of ovarian tissue generally converted progesterone or pregnenolone to androstenedione in high yield but conversion to oestrogen appeared to be low. However, the difficulty of making quantitative comparisons by this method, in the absence of knowledge of the sizes of the pools of endogenous steroids in the tissue, has been recognized. No evidence was found in any of the 18 cases examined for a lack of 3β-hydroxysteroid dehydrogenase. In vitro synthesis of epitestosterone by both normal and polycystic ovaries has been observed. A coincidental granulosa cell tumour in one patient synthesized testosterone in high yield.

1966 ◽  
Vol 52 (3) ◽  
pp. 425-442 ◽  
Author(s):  
Jesus Corral-Gallardo ◽  
Hernan A. Acevedo ◽  
Jose L. Perez de Salazar ◽  
Manuel Loria ◽  
Joseph W. Goldzieher

ABSTRACT Detailed clinical and biochemical studies were performed in a 22 year old woman with primary amenorrhea, virilization, bilateral sclerocystic ovarian disease and a hilar cell tumour of one ovary. By clinical, radiological and dynamic functional endocrine tests, the ovarian source of the excessive androgen production was established prior to surgery. In vivo and in vitro production of testosterone by the tumour was established as well as its ability to metabolize progesterone and 4-androstenedione to a variety of compounds. The biochemical characteristics of this tumour strongly resemble testicular tumours, even to the existence of an 11β-hydroxylase. Epitestosterone was found in the urine, and the existence of a 17α-hydroxysteroid dehydrogenase was demonstrated in the sclerocystic ovarian tissue. No oestrogen was synthesized by the tumour or the ovarian tissue under the in vitro conditions.


2019 ◽  
Vol 104 (12) ◽  
pp. 6182-6192 ◽  
Author(s):  
Lisa Ann Owens ◽  
Stine Gry Kristensen ◽  
Avi Lerner ◽  
Georgios Christopoulos ◽  
Stuart Lavery ◽  
...  

Abstract Context Polycystic ovary syndrome (PCOS) is the most common cause of anovulation. A key feature of PCOS is arrest of follicles at the small- to medium-sized antral stage. Objective and Design To provide further insight into the mechanism of follicle arrest in PCOS, we profiled (i) gonadotropin receptors; (ii) characteristics of aberrant steroidogenesis; and (iii) expression of anti-Müllerian hormone (AMH) and its receptor in granulosa cells (GCs) from unstimulated, human small antral follicles (hSAFs) and from granulosa lutein cells (GLCs). Setting GCs from hSAFs were collected at the time of cryopreservation of ovarian tissue for fertility preservation and GLCs collected during oocyte aspiration before in vitro fertilization/intracytoplasmic sperm injection. Participants We collected hSAF GCs from 31 women (98 follicles): 10 with polycystic ovaries (PCO) and 21 without. GLCs were collected from 6 women with PCOS and 6 controls undergoing IVF. Main Outcome Measures Expression of the following genes: LHCGR, FSHR, AR, INSR, HSD3B2, CYP11A1, CYP19, STAR, AMH, AMHR2, FST, INHBA, INHBB in GCs and GLCs were compared between women with PCO and controls. Results GCs in hSAFs from women with PCO showed higher expression of LHCGR in a subset (20%) of follicles. Expression of FSHR (P < 0.05), AR (P < 0.05), and CYP11A1 (P < 0.05) was lower, and expression of CYP19A1 (P < 0.05), STAR (P < 0.05), HSD3B2 (P = NS), and INHBA (P < 0.05) was higher in PCO GCs. Gene expression in GL cells differed between women with and without PCOS but also differed from that in GCs. Conclusions Follicle arrest in PCO is characterized in GCs by differential regulation of key genes involved in follicle growth and function.


Reproduction ◽  
2020 ◽  
Author(s):  
Ling Jin ◽  
Liang Ren ◽  
Jing Lu ◽  
Xue Wen ◽  
Siying Zhuang ◽  
...  

Polycystic ovary syndrome (PCOS) is a common endocrine disorder accompanied by chronic low-grade inflammation; its etiology is still undefined. This study investigated the expression of CXCL12, CXCR4, and CXCR7 in PCOS rats and their role in regulation of apoptosis. To accomplish this, we established an in vivo PCOS rat model and studied KGN cells (human ovarian granulosa cell line) in vitro. In PCOS rats, the ovarian expression of CXCL12, CXCR4, and CXCR7 was reduced, and the apoptosis rate of granulosa cells was increased, accompanied by decreased expression of BCL2 and increased expression of BAX and cleaved CASPASE3 (CASP3). We further showed that recombinant human CXCL12 treatment upregulated BCL2, downregulated BAX, and cleaved CASP3 in KGN cells to inhibit their apoptosis in a concentration-dependent manner; moreover, the effect of CXCL12 was weakened by CXCR4 antagonist AMD3100 and anti-CXCR7 neutralizing antibody. In conclusion, PCOS rats showed decreased CXCL12, CXCR4, and CXCR7 expression and increased apoptosis rate of ovarian granulosa cells. Further, in human KGN cells, CXCL12 regulated the expression of BAX, BCL2, and cleaved CASP3 to inhibit apoptosis through CXCR4- and CXCR7-mediated signal transmission. These findings may provide a theoretical and practical basis for illuminating the role of proinflammatory cytokines in the pathogenesis of PCOS.


1993 ◽  
Vol 129 (4) ◽  
pp. 311-314 ◽  
Author(s):  
Alexander V Sluijmer ◽  
Maas J Heineman ◽  
Johannes LH Evers ◽  
Frank H de Jong

In a patient with a granulosa cell tumour, stage 1a1, peripheral and ovarian vein blood samples were drawn before, during and after bilateral oophorectomy. Before operation inhibin and follicle-stimulating hormone levels were in the premenopausal range, whereas the peripheral level of oestradiol and luteinizing hormone were in the normal postmenopausal range. In the ovarian vein at the side of the tumour, inhibin and oestradiol levels were elevated, whereas in the contralateral ovarian vein the concentrations of inhibin and oestradiol were in the same range as in the peripheral vein. Immunoreactive inhibin levels in the homogenized tumour were 23 times higher than in the contralateral ovary, whereas inhibin bioactivities in the same samples amounted to 126 and 14 U/mg protein, respectively. After removal of the tumour, peripheral serum follicle-stimulating hormone and inhibin levels were in the normal postmenopausal range again. We conclude that inhibin can have a role as a marker for granulosa cell tumours.


Reproduction ◽  
2008 ◽  
Vol 136 (2) ◽  
pp. 187-194 ◽  
Author(s):  
A I Qureshi ◽  
S S Nussey ◽  
G Bano ◽  
P Musonda ◽  
S A Whitehead ◽  
...  

Histological studies have demonstrated that polycystic ovaries (PCO) contain increased numbers of preantral follicles with a specific increase in primary follicles. Polycystic ovary syndrome is associated with hyperandrogenism and pre- and postnatal androgenisation of primates increases the pool of growing follicles producing changes resembling PCO. In vitro studies could test the hypothesis that androgens alter early folliculogenesis, but conventional culture techniques for small follicles are generally unsuitable in non-rodent species. Our objective was to develop and use a method to investigate the effects of testosterone on early folliculogenesis. We adapted an in ovo technique in which lamb cortical ovarian fragments were grafted onto the chorioallantoic membrane of fertilised chick eggs. Optimal experimental conditions for vascularisation and survival of tissue were determined and the model then used to investigate the effects of testosterone on follicle growth. Eggs were inoculated with testosterone at the time of implantation of the ovarian tissue, which was retrieved 5 days later. Tissue was sectioned and follicles staged and counted. There was no wholesale initiation of primordial follicle growth over the 5-day in ovo culture. Importantly, the proportion of primordial, primary and secondary follicles remained similar to those in unimplanted tissue. Testosterone increased the number of primary follicles by 50% compared with controls, an effect that was largely due to a reduction in atresia. In conclusion, incubation of ovarian cortex with testosterone reproduces the changes in early folliculogenesis reported in histological studies of PCO.


1963 ◽  
Vol 27 (3) ◽  
pp. 327-NP ◽  
Author(s):  
R. V. SHORT ◽  
D. R. SHORTER ◽  
J. L. LINZELL

SUMMARY A case is described of a granulosa cell tumour of the ovary in a virgin heifer, which was showing signs of nymphomania. The cyst fluid from the tumour contained progesterone, 20β-hydroxypregn-4-en-3-one, possibly a trace of 17α-hydroxyprogesterone, and oestradiol-17β. The progesterone: oestradiol-17β ratio was only 6:1, and yet the tumour appeared to have caused normal mammary development and lactation.


1960 ◽  
Vol XXXV (IV) ◽  
pp. 513-517
Author(s):  
W. P. Plate

ABSTRACT The hormone-producing mesenchymomas of the ovaries can be divided into androblastomas and gynaecoblastomas. The former are derived from »male« elements, and consist of Sertoli-cell tumours and Leydig-cell tumours. The latter arise from »female« elements and consist of granulosacell tumours and theca-cell tumours. Sertoli-cell tumours and granulosacell tumours produce oestrogens, while Leydig-cell tumours and theca-cell tumours produce oestrogens or androgens. Histologically, androblastomas and gynaecoblastomas are often difficult to distinguish. Since no »female« elements occur in a testicle, a granulosa-cell tumour in a testicle is improbable. Gynandroblastomas, therefore, can only be found in an ovary.


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