Long-term effects of GnRH agonist, GnRH antagonist, and estrogen plus progesterone treatment on apoptosis related genes in rat ovary

2009 ◽  
Vol 91 (5) ◽  
pp. 2006-2011 ◽  
Author(s):  
Bahadır Saatli ◽  
Sefa Kizildag ◽  
Cemal Posaci ◽  
Erbil Dogan ◽  
Meral Koyuncuoglu ◽  
...  
Keyword(s):  
Gnrh Agonist ◽  
Gnrh Antagonist ◽  
Long Term Effects ◽  
Progesterone Treatment ◽  
Rat Ovary

Suppression of pituitary-testis function in rats treated neonatally with a gonadotrophin-releasing hormone agonist and antagonist: acute and long-term effects

1989 ◽  
Vol 123 (1) ◽  
pp. 83-91 ◽  
Author(s):  
K.-L. Kolho ◽  
I. Huhtaniemi
Keyword(s):  
Body Weight ◽  
Gnrh Agonist ◽  
Gnrh Antagonist ◽  
Long Term Effects ◽  
Adult Rats ◽  
Releasing Hormone ◽  
Serum Lh ◽  
Accessory Sex Organs ◽  
Gonadotrophin Releasing Hormone

ABSTRACT The acute and long-term effects of pituitary-testis suppression with a gonadotrophin-releasing hormone (GnRH) agonist, d-Ser(But)6des-Gly10-GnRH N-ethylamide (buserelin; 0·02, 0·1, 1·0 or 10 mg/kg body weight per day s.c.) or antagonist, N-Ac-d-Nal(2)1,d-p-Cl-Phe2,d-Trp3,d-hArg(Et2)6,d-Ala10-GnRH (RS 68439; 2 mg/kg body weight per day s.c.) were studied in male rats treated on days 1–15 of life. The animals were killed on day 16 (acute effects) or as adults (130–160 days; long-term effects). Acutely, the lowest dose of the agonist decreased pituitary FSH content and testicular LH receptors, but with increasing doses pituitary and serum LH concentrations, intratesticular testosterone content and weights of testes were also suppressed (P< 0·05–0·01). No decrease was found in serum FSH or in weights of accessory sex organs even with the highest dose of the agonist, the latter finding indicating continuing secretion of androgens. The GnRH antagonist treatment suppressed pituitary LH and FSH contents and serum LH (P< 0·05–0·01) but, as with the agonist, serum FSH remained unaltered. Testicular testosterone and testis weights were decreased (P <0·01) but testicular LH receptors remained unchanged. Moreover, the seminal vesicle and ventral prostate weights were reduced, in contrast to the effects of the agonists. Pituitary LH and FSH contents had recovered in all adult rats treated neonatally with agonist and there was no effect on serum LH and testosterone concentrations or on fertility. In contrast, in adult rats treated neonatally with antagonist, weights of testis and accessory sex organs remained decreased (P <0·01–0·05) but hormone secretion from the pituitary and testis had returned to normal except that serum FSH was increased by 80% (P <0·01). Interestingly, 90% of the antagonist-treated animals were infertile. It is concluded that treatment with a GnRH agonist during the neonatal period does not have a chronic effect on pituitary-gonadal function. In contrast, GnRH antagonist treatment neonatally permanently inhibits the development of the testis and accessory sex organs and results in infertility. Interestingly, despite the decline of pituitary FSH neonatally, neither of the GnRH analogues was able to suppress serum FSH values and this differs from the concomitant changes in LH and from the effects of similar treatments in adult rats. Journal of Endocrinology (1989) 123, 83–91

Long-term effects of a gonadotrophin-releasing hormone agonist ([d-Ser(But)6]GnRH(1–9)nonapeptide-ethylamide) on gonadotrophin secretion from human pituitary gonadotroph cell adenomas in vitro

1988 ◽  
Vol 118 (3) ◽  
pp. 491-496 ◽  
Author(s):  
M. Daniels ◽  
P. Newland ◽  
J. Dunn ◽  
P. Kendall-Taylor ◽  
M. C. White
Keyword(s):  
Gnrh Agonist ◽  
In Vitro Release ◽  
Long Term Effects ◽  
Human Pituitary ◽  
Α Subunit ◽  
Releasing Hormone ◽  
Gonadotrophin Secretion ◽  
Gonadotrophin Releasing Hormone

ABSTRACT We have studied the effects of TRH and native gonadotrophin-releasing hormone (GnRH), and of a GnRH agonist (Buserelin; [d-Ser(But)6]GnRH(1–9) nonapeptide-ethylamide), on LH, FSH, α subunit and LH-β subunit secretion from three human gonadotrophin-secreting pituitary adenomas in dispersed cell culture. During a 24 h study, treatment with 276 nmol TRH/1 resulted in a significant (P < 0·05) stimulated release of FSH and α subunit from all three adenomas, and LH from the two adenomas secreting detectable concentrations of this glycoprotein; treatment with 85 nmol GnRH/l significantly (P < 0·05) stimulated the release of α subunit from all three, but FSH from only two and LH from only one adenoma. During a long-term 28-day study, basal FSH and α subunit concentrations were maintained, but secretion of LH, and LH-β (detectable from one tumour only), declined with time from two of the three adenomas. Addition of Buserelin to the cultures resulted in the continuous (P < 0·05) stimulation of α subunit secretion from all three adenomas, and of LH and FSH from two, whilst a transient stimulatory effect on LH and FSH secretion was seen from a third adenoma, with subsequent secretion rates declining towards control values. These data show that human gonadotrophin-secreting adenomas demonstrate variable stimulatory responses to hypothalamic TRH and GnRH, and that during chronic treatment with a GnRH agonist the anticipated desensitizing effect of the drug was not observed in two out of three adenomas studied. The mechanism for this is not clear, but such drugs are unlikely to be of therapeutic value in the management of gonadotrophin-secreting tumours. The data also suggest that GnRH and GnRH agonists have a differential effect on the in-vitro release of intact gonadotrophins and the common α subunit. J. Endocr. (1988) 118, 491–496

scholarly journals Effect of local heating of rat testes after suppression of spermatogenesis by pretreatment with a GnRH agonist and an anti-androgen

Reproduction ◽  
2002 ◽  
pp. 133-140 ◽  
Author(s):  
BP Setchell ◽  
L Ploen ◽  
EM Ritzen
Keyword(s):  
Cross Sections ◽  
Gnrh Agonist ◽  
Local Heating ◽  
Epididymal Sperm ◽  
Long Term Effects ◽  
Sperm Counts ◽  
Pachytene Spermatocytes ◽  
Tubular Diameter ◽  
Testis Mass

The effects of local heating of rat testes, in which spermatogenesis had been suppressed with injections of a GnRH agonist and an anti-androgen, were examined. Although the detrimental effects of heating were not as marked as those found in the testes of non-injected rats, the testes in which spermatogenesis was suppressed also showed a significant reduction in mass, the number of spermatozoa, tubular diameter and the percentage of normal tubular cross-sections at day 35 after heating. The results indicate that heating has an effect on cells in the testis other than those shown to be most susceptible to heat, namely pachytene spermatocytes and early spermatids, which were absent or markedly reduced in number when spermatogenesis was suppressed. The long-term effects of heating on the above parameters, as reported in a previous study, were also confirmed. However, in testes in which spermatogenesis was suppressed at the time of heating, there appeared to be no or a reduced long-term impairment of spermatogenesis, as determined by testis mass, the percentage of qualitatively normal tubules and epididymal sperm counts.

scholarly journals Long-term follow-up of children exposed in-utero to progesterone treatment for prevention of preterm birth: study protocol of the AMPHIA follow-up

BMJ Open ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. e053066
Author(s):  
Noor E Simons ◽  
Emilie V J van Limburg Stirum ◽  
Aleid G van Wassenaer-Leemhuis ◽  
Martijn J J Finken ◽  
Cornelieke S H Aarnoudse-Moens ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Randomised Trial ◽  
Multiple Gestation ◽  
Long Term Effects ◽  
Follow Up Study ◽  
Multiple Gestations ◽  
Progesterone Treatment ◽  
Long Term Follow Up

IntroductionPreterm birth is one of the main problems in obstetrics, and the most important cause of neonatal mortality, morbidity and neurodevelopmental impairment. Multiple gestation is an important risk factor for preterm birth, with up to 50% delivering before 37 weeks. Progesterone has a role in maintaining pregnancy and is frequently prescribed to prevent (recurrent) preterm birth and improve pregnancy outcomes in high-risk patients. However, little is known about its long-term effects in multiple gestations. The objective of this follow-up study is to assess long-term benefits and harms of prenatal exposure to progesterone treatment in multiple gestations on child development.Methods and analysisThis is a follow-up study of a multicentre, double-blind, placebo-controlled randomised trial (AMPHIA trial, ISRCTN40512715). Between 2006 and 2009 women with a multiple gestation were randomised at 16–20 weeks of gestation to weekly injections 250 mg 17α-hydroxyprogesterone caproate or placebo, until 36 weeks of gestation or delivery. The current long-term follow-up will assess all children (n=1355) born to mothers who participated in the AMPHIA trial, at 11–14 years of age, with internationally validated questionnaires, completed by themselves, their parents and their teachers.Main outcomes are child cognition and behaviourAdditional outcomes are death (perinatal and up to age 14), gender identity, educational performance and health-related problems. We will use intention-to-treat analyses comparing experimental and placebo group. To adjust for the correlation between twins, general linear mixed-effects models will be used.Ethics and disseminationAmsterdam UMC MEC provided a waiver for the Medical Research Involving Human Subjects Act (W20_234#20.268). Results will be disseminated through peer-reviewed journals and summaries shared with stakeholders, patients and participants. This protocol is published before analysis of the results.Trial registration numberNL8933.

Blockade of the neonatal increase in testosterone by a GnRH antagonist: the free androgen index, reproductive capacity and postmortem findings in the male marmoset monkey

1997 ◽  
Vol 154 (1) ◽  
pp. 125-131 ◽  
Author(s):  
S F Lunn ◽  
G M Cowen ◽  
H M Fraser
Keyword(s):  
Reproductive System ◽  
Gnrh Antagonist ◽  
Neonatal Period ◽  
Active Form ◽  
Biologically Active ◽  
Sex Hormone Binding Globulin ◽  
Reproductive Capacity ◽  
Control Group ◽  
Long Term Effects

Abstract Male marmoset monkeys which had received gonadotrophin-releasing hormone (GnRH) antagonist treatment as neonates to block the postnatal increase in testosterone were studied, with the object of determining potential long-term effects of treatment on the reproductive system, including tests of fertilising capacity. To obtain information on the nature of the circulating testosterone during this neonatal period, sequential blood samples were collected from a further control group of ten neonates, aged between birth and 3 months, and from 11 adult, normally fertile males, to examine the relative proportions of free, sex-hormone-binding globulin (SHBG)-bound, and non-SHBG-bound testosterone. In control neonates, 11% of the circulating testosterone was free, and a further 19% non-SHBG-bound, and therefore presumed to be biologically available. The remaining 70% was SHBG-bound and considered to be biologically inert. This indicates that the neonatal increase in marmoset testosterone has a biological function. After pairing with females, time to first positive vaginal lavage and first delivery was similar for females, whether they were with control or treated male partners. Pregnancy outcome, in terms of number of young delivered and sex ratio, did not differ. This indicates that there appear to be no long-term sequelae in terms of procreative ability in male marmosets treated neonatally with a GnRH antagonist. Autopsy revealed no gross changes, except in the thymus, which was significantly heavier in the treated group. These results indicate that, although the circulating testosterone is in a biologically active form during the neonatal period, inhibition of testicular function in the neonate is without major effect on the adult male reproductive system. Treatment with a GnRH antagonist may have long-term effects on the immune system. Journal of Endocrinology (1997) 154, 125–131

scholarly journals Long-term effects of deslorelin implants on reproduction in the female tammar wallaby (Macropus eugenii)

Reproduction ◽  
2005 ◽  
Vol 129 (3) ◽  
pp. 361-369 ◽  
Author(s):  
C A Herbert ◽  
T E Trigg ◽  
M B Renfree ◽  
G Shaw ◽  
D C Eckery ◽  
...  
Keyword(s):  
Gnrh Agonist ◽  
Slow Release ◽  
Tammar Wallaby ◽  
Term Treatment ◽  
Long Term Effects ◽  
Macropus Eugenii ◽  
Reproductive Management ◽  
Long Term Treatment ◽  
Negative Side Effects

The contraceptive and endocrine effects of long-term treatment with implants containing the GnRH agonist deslorelin were investigated in female tammar wallabies (Macropus eugenii). Fertility was successfully inhibited for 515 ± 87 days after treatment with a 5 mg deslorelin implant (n= 7), while control animals gave birth to their first young 159 ± 47 days after placebo implant administration (n= 8). The duration of contraception was highly variable, ranging from 344 to 761 days. The strict reproductive seasonality in the tammar wallaby was maintained once the implant had expired. This inhibition of reproduction was associated with a significant reduction in basal LH concentrations and a cessation of oestrous cycles, as evidenced by low progesterone concentrations. There was evidence to suggest that some aspect of either blastocyst survival, luteal reactivation, pregnancy or birth may be affected by deslorelin treatment in some animals. These results show that long-term inhibition of fertility in the female tammar wallaby is possible using slow-release deslorelin implants. The effects of deslorelin treatment were fully reversible and there was no evidence of negative side effects. Slow-release GnRH agonist implants may represent a practicable method for reproductive management of captive and semi-wild populations of marsupials.

scholarly journals Reduction of long-term effects of local heating of the testis by treatment of rats with a GnRH agonist and an anti-androgen

Reproduction ◽  
2001 ◽  
pp. 255-263 ◽  
Author(s):  
BP Setchell ◽  
L Ploen ◽  
EM Ritzen
Keyword(s):  
Gnrh Agonist ◽  
Local Heating ◽  
Seminiferous Tubules ◽  
Long Term Effects ◽  
Adult Rats ◽  
Tissue Mass ◽  
Interstitial Fluid Volume ◽  
Initial Decrease ◽  
Testis Mass

Heating the testes of anaesthetized adult rats to 43 degrees C for 30 min in a waterbath was followed by a large decrease in testis and epididymis mass and number of spermatozoa 35 days later. These parameters had recovered to some extent, but not completely, by days 70 and 97 after heating, but had decreased again in rats examined on day 182. There were no consistent effects of heating on androgen status, as determined by the concentrations of testosterone in blood and testis fluids, or by seminal vesicle mass, and interstitial fluid volume was increased in the heated testes. Treatment of rats with an implant of a GnRH agonist and daily injections of an anti-androgen for 14 days (sufficient in itself to cause large temporary decreases in tissue mass, number of spermatozoa and androgen status) did not reduce the initial decrease in testis mass or number of spermatozoa seen after heating, but reduced the later decreases in mass and number of spermatozoa significantly. These findings indicate that, as well as causing damage to spermatocytes and spermatids, as previously reported, heating also reduces the ability of spermatogonia to repopulate the seminiferous tubules at longer intervals after heating. Furthermore, it appears that this effect on the spermatogonia can be reduced by treating the animals with a GnRH agonist and anti-androgen, a treatment similar to that shown by other authors to improve recovery of the testis from irradiation or drug treatment.

Ovarian Dysfunction in Fetally Irradiated Beagles

1977 ◽  
Vol 35 ◽  
pp. 658-659
Author(s):  
T. M. Seed ◽  
M. H. Sanderson ◽  
D. L. Gutzeit ◽  
T. E. Fritz ◽  
D. V. Tolle ◽  
...  
Keyword(s):  
Gamma Rays ◽  
Low Dose ◽  
Long Term Effects ◽  
Ovarian Dysfunction ◽  
Dose Rates ◽  
Highly Sensitive ◽  
Microscopic Evaluation ◽  
Ovarian Pathology ◽  
Normal Offspring

The developing mammalian fetus is thought to be highly sensitive to ionizing radiation. However, dose, dose-rate relationships are not well established, especially the long term effects of protracted, low-dose exposure. A previous report (1) has indicated that bred beagle bitches exposed to daily doses of 5 to 35 R 60Co gamma rays throughout gestation can produce viable, seemingly normal offspring. Puppies irradiated in utero are distinguishable from controls only by their smaller size, dental abnormalities, and, in adulthood, by their inability to bear young.We report here our preliminary microscopic evaluation of ovarian pathology in young pups continuously irradiated throughout gestation at daily (22 h/day) dose rates of either 0.4, 1.0, 2.5, or 5.0 R/day of gamma rays from an attenuated 60Co source. Pups from non-irradiated bitches served as controls. Experimental animals were evaluated clinically and hematologically (control + 5.0 R/day pups) at regular intervals.

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