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- Svensson, Per-Arne, 1969, et al.
(författare)
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Scavenger receptor class B type I in the rat ovary: possible role in high density lipoprotein cholesterol uptake and in the recognition of apoptotic granulosa cells.
- 1999
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 140:6, s. 2494-500
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Tidskriftsartikel (refereegranskat)abstract
- Scavenger receptor class B type I (SR-BI) mediates the selective uptake of high density lipoprotein cholesterol. SR-BI is expressed at high levels in the ovary, indicating that it plays a role in the delivery of cholesterol as substrate for steroid hormone production. However, SR-BI also binds anionic phospholipids with high affinity and could therefore be involved in the recognition of apoptotic cells. In this study we have characterized the expression of SR-BI in rat ovarian follicles undergoing atresia. Atretic follicles with cells undergoing apoptosis were identified by in situ DNA end labeling, and SR-BI expression was determined by in situ hybridization and immunohistochemistry. SR-BI was expressed in thecal cells at all stages of follicular development, including atretic follicles, and in corpus luteum. Isolated apoptotic granulosa cells (but not viable granulosa cells) bound annexin V, indicating that they display anionic phospholipids on the cell surface. Transfection of COS-7 cells with an expression vector carrying the rat SR-BI complementary DNA resulted in increased binding to apoptotic granulosa cells (46 +/- 2% of the SR-BI-expressing cells bound at least one granulosa cell compared with 24 +/- 3% for the mock-transfected cells; P < 0.0001), whereas the binding to viable granulosa cells was unchanged. Apoptotic granulosa cells also bound to isolated thecal shells. We conclude that thecal cells of both nonatretic and atretic follicles express SR-BI. The location of SR-BI expression in the ovary supports a role of this receptor in the uptake of high density lipoprotein cholesterol. In addition, our data suggest that SR-BI mediates the recognition of apoptotic granulosa cells by the surrounding thecal cells and that it therefore may play a role in the remodeling of atretic follicles to secondary interstitial cells.
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- Boguszewski, C L, et al.
(författare)
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Circulating non-22-kilodalton growth hormone isoforms in acromegalic men before and after transsphenoidal surgery.
- 1997
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 82:5, s. 1516-21
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Tidskriftsartikel (refereegranskat)abstract
- GH represents several molecular isoforms in addition to the main 22-kDa (22K) GH. There have been reports suggesting that circulating non-22K GH isoforms are increased in acromegaly, but the possible implications of such observations in the management of the disease have not been addressed. The aim of this study was to evaluate the proportion of circulating non-22K GH isoforms in acromegaly. In addition, the relationships between the amount of non-22K GH and tumor size, biochemical measurements, and body composition also were investigated. Samples with different GH levels were selected from 24-h GH profiles from 15 acromegalic men evaluated before and 1 yr after transsphenoidal surgery and from 13 healthy men. The serum non-22K GH levels, expressed as percentage of total GH concentration, were determined by the 22K GH exclusion assay, which is based on immunomagnetic extraction of 22K GH from serum and quantitation of non-22K GH using a polyclonal GH assay. The proportion of non-22K GH isoforms was fairly constant in different samples from the same patient, regardless of the GH level. However, a wide variation of values was observed among acromegalics, both before (14-51%) and after surgery (8-62%). The proportion of non-22K GH isoforms was increased in untreated patients, compared with controls (26.6 vs. 17.4%; P < 0.01), and the values correlated significantly to tumor size, mean 24-h GH concentration, serum PRL, and extracellular water. After surgery, patients not truly cured, with mean 24-h GH concentration of 1 microg/L or more, had an increased proportion of non-22K GH, compared with those with levels less than 1 microg/L (P < 0.01). In the former group, the median values were similar than those in untreated acromegalics (34 vs. 26.6%, respectively), whereas in the latter, they were comparable with those in the controls (15.2 vs. 17.4%, respectively). We conclude that acromegalics have an increased proportion of circulating non-22K GH isoforms. The values are fairly constant in different samples from an individual, regardless of GH level, but a large spectrum can be observed among patients. This variability suggests that different pituitary adenomas secrete GH isoforms in variable amounts. Our observation that a higher proportion of non-22K GH isoforms is present in patients not truly cured after surgery suggests that the evaluation of non-22K GH isoforms can be useful in the follow-up of acromegalic patients.
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- Boguszewski, C L, et al.
(författare)
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Cloning of two novel growth hormone transcripts expressed in human placenta.
- 1998
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 83:8, s. 2878-85
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Tidskriftsartikel (refereegranskat)abstract
- Several isoforms of human GH (hGH) are produced by two related genes expressed in the pituitary (hGH-N) and in the placenta (hGH-V). These genes consist of five exons (denoted 1-5) separated by four introns (denoted A-D). In the present report, two new transcripts of the hGH-V gene are described. The coding region of the hGH-V gene was amplified by RT-PCR using placental complementary DNA as template. DNA sequencing of several clones revealed two novel transcripts. One had a 45-bp deletion caused by the use of an alternative splice acceptor site within exon 3, similar to that in the hGH-N gene, predicting a 20-kDa isoform of hGH-V. The other transcript was generated by the use of an alternative splice donor site causing a 4-bp deletion in the end of exon 4, predicting a 24-kDa protein with 219 amino acids, which we refer to as hGH-V3. The carboxy-terminal sequence of hGH-V3 differs from 22-kDa hGH-V and hGH-V2, the two previously reported transcripts of the hGH-V gene, and does not contain a predicted transmembrane domain as described for hGH-V2. Ligase chain reaction was then used to analyze the possible use of the same splicing pattern in transcripts derived from the other genes of the hGH-gene cluster. Alternatively spliced transcripts encoding the 20-kDa hGH isoform were detected from the hGH-N and hGH-V genes, but not from the human chorionic somatomammotropin-A/B genes. The alternative splicing generating hGH-V3 was only demonstrated in transcripts derived from the hGH-V gene. Using competitive RT-PCR, the expression of hGH-V3 was estimated to be 10% of the hGH-V messenger RNA in full-term normal placentas and in placentas from pathological pregnancies. The 20-kDa hGH-V was detected in two of four full-term normal placentas, whereas a weak signal was observed in one of the pathological placentas. We conclude that the hGH-V primary transcript undergoes alternative splicing pathways generating at least four different messenger RNAs, predicting the expression of different hGH isoforms, including two with a complete sequence divergence in the carboxy-terminus.
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