[Dementia--research results give hope for treatment].
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Aged↗
Biomedical subjects
L Rönnberg
Publications and source records attributed to L Rönnberg.
Laminin in the human embryo implantation: analogy to the invasion by malignant cells.
OBJECTIVE: To explore the possible similarities between the biochemical processes of embryo implantation and malignant invasion. DESIGN: The expression of a basement membrane (BM) glycoprotein laminin, a matrix binding cell surface receptor protein beta 1-integrin, and a BM collagen degrading metalloproteinase type IV collagenase, was studied in cultured human in vitro fertilized embryos. PATIENTS: Eight healthy women suffering from tubal infertility were participating in the IVF program in the Department of Obstetrics and Gynecology in University Hospital of Oulu. Twenty oocytes and 110 pre-embryos that were not transferred for the fertilizations were used in this study. MAIN OUTCOME MEASURES: Fibronectin, laminin, beta 1-integrin, and type IV collagenase immunoreactive proteins were studied in embryos by immunoperoxidase staining, and type IV collagen degrading activity was measured from the culture media of the embryos. RESULTS: Laminin and beta 1-integrin were expressed in the early human embryos before the time of implantation. Type IV collagen degrading activity and the 72 kd-type IV collagenase immunoreactive protein were expressed at the time of implantation. Laminin supported the expression of type IV collagenase. CONCLUSIONS: The expression of laminin, beta 1-integrin, and type IV collagenase in vitro are temporally in good correlation with the time of the implantation in vivo. Laminin and beta 1-integrin can relate to the attachment of the embryos to the uterine BM and type IV collagenase to the degradation of the BM collagen during the implantation. Laminin can augment the process locally.
Adult↗
Effect of growth hormone administration on human ovarian function and steroidogenic gene expression in granulosa-luteal cells.
OBJECTIVE: To study the effect of growth hormone (GH) in combination with an ultrashort-term gonadotropin-releasing hormone analogue/human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) regimen in ovarian hyperstimulation for in vitro fertilization (IVF). DESIGN: Prospective randomized placebo-controlled study. SETTING: University-based IVF program. PATIENTS: Fifty-four normally cycling women (27 control and 27 GH-treated) participated in this study. INTERVENTIONS: Human recombinant GH (24 IU)/placebo was given intramuscularly on alternate days starting on cycle day 4 until the day of last hMG injection. RESULTS: Serum estradiol (E2) and progesterone (P) concentrations were slightly lower in the GH group than in the placebo group on the day of hCG injection and 1 day thereafter (P < 0.01 to 0.001). Serum luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone (T), and sex hormone-binding globulin did not differ between the groups. The follicular fluid (FF) concentration of T was higher in the GH group than in the placebo group (15.9 +/- 6.0 nmol/L versus 10.2 +/- 4.9 nmol/L, P < 0.005), and no differences were observed in the FF concentrations of E2, P, and insulin-like growth factor I between the groups. In granulosa cells isolated from patients who received GH treatment, the levels of 3 beta-hydroxysteroid dehydrogenase and aromatase messenger ribonucleic acid were significantly higher than in the patients receiving placebo. The number of hMG ampules needed for follicular development and the number of follicles and oocytes recovered were similar in both groups. CONCLUSIONS: These results indicate that GH administration modifies ovarian steroidogenic response to gonadotropins in IVF patients, suggesting a role for GH in the regulation of human ovarian function.
Adult↗
Ectopic pregnancy and infertility following treatment of infertile couples: a follow-up of 929 cases.
A follow-up analysis was made of 929 infertile couples, with special attention paid to ectopic pregnancy. The conception rate was 46%, and 9% of the pregnancies were ectopic. Previous ectopic pregnancy, an industrial occupation and smoking reduced the fecundity and increased the risk of ectopic pregnancy. Tubal damage as a verified reason for infertility and its treatment also increased the risk of ectopic pregnancy. Stepwise logistic regression analysis showed the strongest association with ectopic pregnancy to exist in the case of women with a previous ectopic pregnancy (9.9-fold risk) rather than women with primary infertility. Treatment of tubal damage by salpingostomy entailed a 6.0-fold risk and treatment by other methods a 2.8-fold risk. Women working in industry had a 3.5-fold risk of ectopic pregnancy compared with those in other professions.
Abortion, Spontaneous↗
[Endometriosis and infertility].
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Endometriosis↗
Regulation of steroid and steroid sulfate production and aromatase activity in cultured human granulosa-luteal cells.
The regulation of the production of steroids and steroid sulfates and the activity of aromatase in human luteinized granulosa cells were investigated. The cells were cultured for 48 h in the presence or absence of hCG and FSH. Basal production of pregnenolone (Pre, 0.3 +/- 0.03 ng/micrograms protein) and progesterone (P, 19.3 +/- 1.7 ng/micrograms protein) were high compared with that of other steroids beyond P in the steroidogenic pathway. The concentration of 17 alpha-hydroxyprogesterone (17-OHP) was lower 0.17 +/- 0.06 ng/micrograms and that of other steroids in the 4-ene and 5-ene pathways and steroid sulfates less than 0.05 ng/micrograms. Both hCG and FSH (100 ng/ml) stimulated the production of Pre and P 3- to 5-fold, but only minimal stimulation of other steroids and steroid sulfates was observed. Aromatase activity of granulosa-luteal cells was measured from the rate of formation of 3H2O from 1 beta-[3H]androstenedione (1 beta[3H]A) after exposing the cells to hCG, FSH or estradiol (E2) for 48 h. Basal aromatase activity was relatively low, but hCG and FSH stimulated aromatase 8- and 4-fold, respectively. The incubation of granulosa-luteal cells with E2 did not affect basal aromatase activity, but E2 augmented FSH-stimulated aromatase 1.4-fold (P less than 0.025). The results suggest that there is low 17 alpha-hydroxylase and steroid sulfokinase activity in human granulosa-luteal cells. Aromatase activity in these cells is regulated by both hCG and FSH, and intra-ovarian estrogens may regulate granulosa cell aromatase activity.
Aromatase↗
Gonadotropin pulsatility in a stimulated cycle: clomiphene citrate increases pulse amplitudes of both luteinizing hormone and follicle-stimulating hormone.
OBJECTIVE: To elucidate gonadotropin secretory patterns during ovarian hyperstimulation for in vitro fertilization. DESIGN: All volunteers who attended the unit during a period of 3 months were prospectively investigated. SETTING: Infertility unit of the University Central Hospital of Oulu. PARTICIPANTS: Normally menstruating tubal infertility patients (n = 8) and healthy women with ovulatory cycles (hospital personnel, n = 11). All patients finished the study. INTERVENTIONS: Clomiphene citrate (CC), 50 mg, was administered on cycle days 5 to 9 and 300 IU of pure follicle-stimulating hormone (FSH) on cycle day 7 and 150 IU on cycle day 8. MAIN OUTCOME MEASURES: Serum samples for luteinizing hormone (LH) and FSH measurements were collected at 10-minute intervals for 6 hours on cycle day 7 (effect of CC) and day 9 (effect of CC/FSH), and the data were analyzed with the Munro computer program. RESULTS: The number of LH peaks was identical in the controls and study subjects on cycle days 7 and 9, whereas the pulse amplitude (P less than 0.025) and the pulse area (P less than 0.01) were higher in the CC/FSH-treated patients. The increase in overall mean LH level during the hormone therapy was not significant. In the CC/FSH-treated women, a decreased number of FSH pulses (P less than 0.01) with increased amplitude (P less than 0.001) and pulse area (P less than 0.01) was found. Clomiphene citrate treatment increased the mean FSH level (control versus cycle day 7, P less than 0.05) which was further increased (cycle day 7 versus cycle day 9, P less than 0.05) by FSH administration on cycle days 7 to 8. Otherwise pure FSH was found to be unable to modify endogenous LH or FSH secretory patterns under these conditions. CONCLUSIONS: Clomiphene citrate increases the amplitudes of both LH and FSH pulses in the midfollicular phase of a stimulated cycle, an effect which is not influenced by pure FSH administration.
Adult↗
Insulin-like growth factor binding protein-1 and ovarian stimulation.
Serum concentrations of insulin-like growth factor binding protein-1 (IGFBP-1) were measured in 42 patients with tubal infertility undergoing two different regimens of ovarian stimulation for in-vitro fertilization. The first group comprised 24 women given a luteinizing hormone-releasing hormone agonist analogue (buserelin, LHRHa) on cycle days 1-4 followed by follicle-stimulating hormone and human menopausal gonadotrophin (LHRHa group). The second group of 18 women received clomiphene citrate and gonadotrophins (CC group). On the day of human chorionic gonadotrophin administration, the sum of follicular diameters (P less than 0.05) and the number of follicles punctured in the LHRHa group (P less than 0.01) were significantly higher than in the CC group. In spite of the greater number of follicles, the oestrogen levels were similar in both groups, but women in the LHRHa group had significantly higher serum IGFBP-1 concentrations during the last 5 days of stimulation. These results suggest that the stimulated preovulatory follicles may contribute to the elevation of serum IGFBP-1.
Adult↗
Short and long term effects of growth hormone on circulating levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-1, and insulin: a placebo-controlled study.
The short and long term effects of GH on serum concentrations of insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin were investigated in women participating in an in vitro fertilization program. In this placebo-controlled study, sterile saline (eight women) or 24 IU GH (eight women) were given im on alternate days, starting on cycle day 4, in combination with GnRH and human menopausal gonadotropin. IGFBP-1 levels decreased significantly during the first 4 h after GH administration, whereas no significant changes were seen in the placebo group. The concentrations of serum IGF-I and insulin did not change during 4 h after GH injection. During the 11-day follow-up period, serum levels of both IGF-I and insulin were significantly higher in GH-treated than in placebo-treated women. These results suggest that the serum concentration of IGFBP-1 is not completely GH independent. They also support the earlier findings that long term treatment with GH increases serum IGF-I and insulin levels.
Adult↗
Immunohistochemical localization of carbonic anhydrase isoenzymes in the human male reproductive tract.
The distribution of human carbonic anhydrase (HCA) isoenzymes I, II and VI in the human male reproductive tract was studied using specific antisera against affinity purified isoenzymes in conjunction with the peroxidase-antiperoxidase complex method. HCA VI-specific staining could not be demonstrated in any of the tissues studied, and HCA I was observed only in red blood cells. Immunostaining denoted HCA II in the epithelia of the seminal vesicle, ampulla of the ductus deferens and distal ductus deferens. Some cells in the epithelium of the corpus and cauda epididymidis also stained for HCA II. The staining for HCA II in the epithelium of the reproductive tract declined from the strongly positive seminal vesicle to the proximal part of the ductus deferens, which stained negatively. There were also HCA II-positive particles derived from the apical protrusions of the epithelium in the lumina of the seminal vesicle, ampulla of the ductus deferens and ductus deferens. The physiological role of HCA II is linked to the secretion of bicarbonate into the seminal plasma and thereby to the regulation of sperm motility and pH in the seminal plasma.
Carbonic Anhydrases↗
Endocrine responses to gonadotrophins after LHRH agonist administration on cycle days 1-4: prevention of premature luteinization.
A treatment regime comprising an intranasally administered luteinizing hormone-releasing hormone (LHRH) agonist analogue (buserelin) on cycle days 1-4, followed by gonadotrophin administration [follicle stimulating hormone (FSH)/human menopausal gonadotrophin (HMG)] resulted in identical oestradiol (E2) responses compared with the reference method using clomiphene citrate (CC) and gonadotrophins. Immediately after analogue administration (day 4), buserelin-treated women showed short-lived elevations in serum LH and progesterone concentrations, but in the later follicular phase, the serum LH concentration was lowered compared with the controls. None of the women treated with analogue displayed elevated serum LH or progesterone concentrations at the time of injection of human chorionic gonadotrophin. In the early luteal phase, these women had higher serum levels of progesterone and higher progesterone to E2 ratios than the controls, but the length of the luteal phase was slightly shortened. Hence, in hyperstimulated cycles, 4-day treatment with buserelin caused profound endocrinological changes: namely, short-term rescue of the corpus luteum, prevention of an endogenous LH rise and premature luteinization and increased progesterone production in the early luteal phase.
Adult↗
The ratios of serum bioactive/immunoreactive luteinizing hormone and follicle-stimulating hormone in various clinical conditions with increased and decreased gonadotropin secretion: reevaluation by a highly sensitive immunometric assay.
Serum bioactive and immunoreactive LH and FSH were measured in clinical conditions with increased or decreased gonadotropin secretion. Gonadotropin immunoreactivity was measured using a conventional RIA (I) and an ultrasensitive immunofluorometric method (F). Bioactive (B) LH was assessed by the mouse interstitial cells in vitro bioassay, and B-FSH using the immature rat granulosa cell assay. Acute GnRH stimulation of adult men (n = 6) increased LH levels measured by the different methods 4.3- to 5.3-fold. The B/I ratio of LH increased from 2.34 +/- 0.21 to 3.71 +/- 0.36 (mean +/- SEM) at 120 min (P less than 0.05), but no change was found in the B/F ratio. After ovariectomy of premenopausal women (n = 6), the LH levels increased in 1 week 4- to 6-fold, the B/I ratio from 1.85 +/- 0.22 to 2.59 +/- 0.24, and the B/F ratio from 1.78 +/- 0.22 to 2.90 +/- 0.30 (P less than 0.05 for both). In addition, the LH levels were measured during GnRH agonist treatment of ovarian carcinoma (n = 8), endometriosis (n = 8), and prostatic carcinoma after orchiectomy (n = 8). In the two former groups, serum B-LH decreased in 1 month to undetectable levels (less than 0.5 IU/L), and in the prostate cancer patients to 1.2 (0.8-1.9) IU/L (log mean and range of +/- SEM). The concomitant decline of I-LH was to 1.5-1.9 IU/L in the agonist-treated female patients, and that of F-LH to 0.10-0.15 IU/L; in the prostate cancer patients, respectively, these values were 7-8 and 0.3-0.7 IU/L. The B/I and B/F ratios during the agonist treatments could only be calculated in the prostate cancer patients (in the others, B-LH became undetectable). The B/I ratio decreased from 2.34 +/- 0.5 to 0.14 +/- 0.03 (P less than 0.01), but no suppression was found in the B/F ratio from a pretreatment value of 3.6 +/- 0.8. B-, I-, and F-FSH levels were measured in the GnRH agonist-treated orchiectomized prostate cancer patients. The pretreatment level of B-FSH was 154 (137-175), that of I-FSH was 38.0 (34.4-42.0), and that of F-FSH was 39.8 (35.3-44.9) IU/L. The B/I ratio of FSH was 3.76 +/- 0.49, and the B/F ratio was 3.53 +/- 0.59. The mean B-FSH level decreased during treatment by 87-93.5%, that of I-FSH by 98%, and that of F-FSH by 91.5% (P less than 0.01 for all).(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Circadian and seasonal variation in human preovulatory follicular fluid melatonin concentration.
The concentrations of melatonin in 112 preovulatory follicular fluid (FF) samples obtained from 60 women undergoing in vitro fertilization and 27 patients at laparotomy during a spontaneous cycle were measured by RIA and compared with those in peripheral serum. The circadian and seasonal variations in FF melatonin were also analyzed. The FF melatonin concentrations in stimulated (mean +/- SEM, 61.9 +/- 6.4 pmol/L) and spontaneous cycles (98.1 +/- 8.9 pmol/L) were significantly higher (P less than 0.005) than those in peripheral serum (25.4 +/- 1.2 and 38.6 +/- 1.8 pmol/L, respectively), and in the stimulated cycles there was a positive correlation between them. The FF melatonin concentration in the morning (58.9 +/- 3.8 pmol/L) was significantly higher (P less than 0.005) than that in the daytime (23.2 +/- 0.8 pmol/L), but the morning concentrations did not differ between the light and the dark seasons of the year, whereas the daytime values were higher (P less than 0.005) during the dark season (27.1 +/- 2.1 pmol/L) than during the light season (21.1 +/- 2.1 pmol/L). The FF melatonin concentration did not correlate with follicular volume, and FF and serum melatonin concentrations showed no significant correlation with the serum concentrations of estradiol, progesterone, testosterone, or PRL. There were also no differences between FF melatonin concentrations in aspirates with or without an ovum. In summary, significant circadian and circannual variations in high FF melatonin concentrations were found, which suggest that melatonin could potentially interfere with the regulation of reproduction in humans at the follicular level.
Chromatography, High Pressure Liquid↗
Endometriosis and infertility.
The relationship of endometriosis, the most common benign gynaecological disease during reproductive life, to infertility is generally ill understood. The association between infertility and minimal to mild endometriosis, when no anatomical defect is evident, may be explained by the following possible mechanisms: alternations in peritoneal fluid (macrophages - immunoglobulins, Interleukin-1, protease inhibitors, prostanoids, an ovum capture inhibitor), ovulatory dysfunctions (anovulation, LUF syndrome), luteal phase defect, disturbed implantation, and spontaneous abortion. These possibilities are discussed. The latest prospective controlled studies offer strong evidence that endometriosis per se is not a direct cause of infertility. On the other hand, the disease usually deteriorates if not treated, and therefore medical or surgical interventions are often needed when expectant treatment or other infertility therapies, e.g., ovulation induction, fail to result in pregnancy. Women with minimal to mild endometriosis only should be diagnosed as having unexplained infertility, which today may be treated by in vitro fertilization.
Endometriosis↗
Elevated serum levels of endometrial secretory protein PP14 in patients with advanced endometriosis. Suppression by treatment with danazol and high-dose medroxyprogesterone acetate.
The circulating concentration of endometrial protein PP14 varied during the menstrual cycle in patients with endometriosis. The highest levels were found on days 1 to 4 of the cycle (176 +/- 123 micrograms/L; mean +/- SD), and the lowest on days 5 to 20 (44.1 +/- 29.7 micrograms/L). Rising levels were observed on days 21 to 30 (58.3 +/- 62.6 micrograms/L). On days 5 to 20 (i.e., during period of the lowest levels) patients with advanced endometriosis had higher PP14 levels (63.9 +/- 39.0 micrograms/L) than those with mild endometriosis (29.3 +/- 18.2 micrograms/L; p less than 0.01). Patients with mild endometriosis had slightly higher serum PP14 levels than apparently healthy control subjects (p less than 0.05), but overlapping of values between the two groups is remarkable. Conservative surgical elimination of endometriosis significantly decreased the serum PP14 levels. Treatment with danazol (600 mg/day), or with medroxyprogesterone acetate (100 mg/day) after laparoscopy also resulted in significant decreases in the serum PP14 concentration. After 6 months of treatment, conservative surgery in combination with danazol or with medroxyprogesterone acetate, yielded more pronounced declines in serum PP14 level than conservative surgery plus placebo. No significant difference was observed between the effects of danazol and medroxyprogesterone acetate. We conclude that endometriosis tissue contributes to the circulating PP14 level, and the decline in PP14 level during danazol and medroxyprogesterone acetate treatments reflects regression of intrauterine and ectopic endometrial tissues.
Adult↗
Circulating lipid and lipoprotein concentrations during danazol and high-dose medroxyprogesterone acetate therapy of endometriosis.
In a study on endometriosis, ten patients were treated with danazol (200 mg three times a day) and ten patients with high-dose medroxyprogesterone acetate (MPA) (100 mg a day) for 6 months. The circulating high-density lipoprotein-cholesterol concentration decreased significantly in the danazol (53%) and in the MPA groups (26%); the change in the danazol group was significantly higher than that in the MPA group. Danazol also significantly increased the low-density lipoprotein-cholesterol levels (37%), whereas MPA had no significant effect. Danazol (29%) and MPA (12%) decreased the apolipoprotein A-1 levels significantly. The decrease caused by danazol was significantly greater. Danazol also significantly decreased the apolipoprotein A-2 levels (12%) and significantly increased the apolipoprotein B levels (17%), whereas MPA had no significant effects on them. Three months after the end of medication, all values were at the pretreatment levels. The circulating cholesterol, triglyceride, and very low-density lipoprotein concentrations remained unchanged during both treatments. Danazol and high-dose MPA induced a similar significant regression of peritoneal endometriotic implants in relation to placebo. Our present results, showing that danazol, to a greater extent than high-dose MPA, is associated with changes in lipoprotein metabolism that expose the individual to an increased risk of cardiovascular diseases, suggest that high-dose MPA is preferable to danazol in the long-term treatment of endometriosis.
Adult↗
Prolactin suppression by bromocriptine stimulates aromatization of testosterone to estradiol in women.
The effect of follicular phase bromocriptine therapy on the ovarian endocrine response to clomiphene citrate and gonadotropins was studied in 35 tubal infertility patients in a randomized placebo-controlled trial. During bromocriptine treatment, the serum prolactin (PRL) concentration significantly decreased, and consequently the serum estradiol (E2) concentration was significantly higher than in the controls on cycle day 9, and the ratio of testosterone (T) to E2 was decreased from cycle day 8 through day 10. The luteal phase progesterone concentration and the length of the luteal phase were not affected by bromocriptine therapy. The number and quality of oocytes harvested and the cleavage rates were similar in both groups. The present results, together with our previous observations, demonstrate that PRL participates in the regulation of ovarian steroidogenesis, particularly aromatization of T to E2.
Adult↗
The human embryo produces basement membrane collagen (type IV collagen)-degrading protease activity.
The biochemical basis and mechanism of embryo implantation is poorly understood. The human embryo has to penetrate the endometrial basement membrane and the thick decidual wall during implantation, a process which resembles the active spreading of invasive tumour cells where the degradation of type IV collagen (basement membrane collagen) plays an important role. This study reports that human embryos produce type IV collagen-degrading enzyme activity and the secretion of this enzyme increases with time in culture. The type IV collagen-degrading enzyme activity might facilitate the penetration of the embryo through the decidua, thus emphasizing an active role of the embryo in implantation. On the other hand, unfertilized oocytes secrete low, stable amounts of type IV collagen-degrading enzyme activity in vitro. It was also found that follicular granulosa cells secrete high amounts of type IV collagenolytic activity in culture. It has been previously shown that there is a pre-ovulatory peak in type IV collagenolytic activity in follicular fluid, and it can be assumed that the appearance of this enzyme in the follicular fluid is probably connected to follicular rupture and that it is produced by granulosa cells.
Basement Membrane↗