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

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

scholarly journals Effects of a long-acting gonadotrophin-releasing hormone agonist (Leuprolide) on ovarian follicular development in prepubertal heifer calves

1994 ◽  
Vol 74 (4) ◽  
pp. 649-656 ◽  
Author(s):  
A. C. O. Evans ◽  
N. C. Rawlings
Keyword(s):  
Gnrh Agonist ◽  
Follicular Development ◽  
Ovarian Follicles ◽  
Follicular Growth ◽  
Long Term Effects ◽  
Releasing Hormone ◽  
Gonadotrophin Secretion ◽  
Gonadotrophin Releasing Hormone ◽  
Ovarian Follicular Development ◽  
Ovarian Follicular Growth

We studied the effects of reducing gonadotrophin secretion on ovarian follicular development in young prepubertal heifer calves. Calves received a GnRH agonist (n = 5, 15 mg of Leuprolide acetate, i.m.) or carrier (n = 5) at 8 and 12 w of age. Starting at 8 and 34 w of age, ovarian follicles were monitored daily for 17 d, and at 10, 15, 25 and 35 w of age, blood samples were collected every 15 min for 12 h for measurement of serum concentration of LH and FSH. GnRH agonist treatment did not affect the age and body weight at puberty (P > 0.05). Agonist treatment suppressed follicle numbers and in two heifers follicle emergence (growth above 4–5 mm) was blocked immediately. In three agonist-treated heifers, follicle emergence was blocked after one extended wave of follicular growth. At 34 w of age the pattern of ovarian follicular growth did not differ between groups but oestradiol secretion was lower in agonist-treated heifers. During agonist treatment basal and mean concentrations of FSH, and LH and FSH pulse amplitude were decreased but basal LH concentrations increased (P < 0.05). At 25 and 35 w of age some rebound in gonadotrophin secretion was seen.We concluded that disrupting gonadotrophin secretion in young prepubertal heifer calves by GnRH agonist treatment, suppressed ovarian follicular growth but that a rebound in gonadotrophin secretion prevented long term-effects on sexual development. Key words: Follicle stimulating hormone, gonadotrophin-releasing hormone, heifer calves, luteinising hormone ovarian follicles

Effect of long-term inhibition of gonadotrophin secretion by the gonadotrophin-releasing hormone agonist, buserelin, on sex steroid secretion and ovarian morphology in polycystic ovary syndrome

1990 ◽  
Vol 125 (2) ◽  
pp. 317-325 ◽  
Author(s):  
A. F. Macleod ◽  
M. J. Wheeler ◽  
P. Gordon ◽  
C. Lowy ◽  
P. H. Sönksen ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Gnrh Agonist ◽  
Polycystic Ovary ◽  
Normal Subjects ◽  
Sex Hormone Binding Globulin ◽  
Plasma Testosterone ◽  
Ovary Syndrome ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone

ABSTRACT In order to investigate the effect of long-term suppression of the gonadotrophin axis in polycystic ovary syndrome, eight affected subjects were given s.c. infusions of gonadotrophin-releasing hormone (GnRH) agonist buserelin for 12 weeks. Hormone measurement and ultrasound studies were carried out weekly, from 6 weeks before to 12 weeks after administration of buserelin. An overnight dexamethasone-suppression test was carried out before and after treatment. Maximal suppression of LH to below the lower limit of that in normal subjects occurred after 6 weeks of treatment with buserelin. Plasma testosterone and androstenedione fell to normal levels during the infusion but reached pretreatment levels during the follow-up period. There was no effect of buserelin on plasma dehydroepiandrosterone sulphate or sex hormone-binding globulin. Ovarian size decreased significantly during the infusion with the disappearance of cysts in six subjects. After cessation of buserelin therapy, there was rapid and spontaneous ovulation which occurred within 3 weeks in all subjects. The results suggest that treatment with this GnRH agonist facilitates ovulation in this condition. Journal of Endocrinology (1990) 125, 317–325

Effects of crude and highly purified bovine inhibin (Mr 32 000 form) on gonadotrophin production by ovine pituitary cells in vitro: inhibin enhances gonadotrophin-releasing hormone-induced release of LH

1990 ◽  
Vol 127 (1) ◽  
pp. 149-159 ◽  
Author(s):  
S. Muttukrishna ◽  
P. G. Knight
Keyword(s):  
Primary Cultures ◽  
Suppressive Effect ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
Α Subunit ◽  
Releasing Hormone ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone

ABSTRACT Primary cultures of ovine pituitary cells (from adult ewes) were used to investigate the actions of steroid-free bovine follicular fluid (bFF) and highly-purified Mr 32 000 bovine inhibin on basal and gonadotrophin-releasing hormone (GnRH)-induced release of FSH and LH. Residual cellular contents of each hormone were also determined allowing total gonadotrophin content/well to be calculated. As in rats, both crude and highly purified inhibin preparations promoted a dose (P < 0·001)- and time (P < 0·001)-dependent suppression of basal and GnRH-induced release of FSH as well as an inhibition of FSH synthesis, reflected by a fall in total FSH content/well. However, while neither inhibin preparation affected basal release of LH or total LH content/well, GnRH-induced LH release was significantly (P< 0·001) increased by the presence of either bFF (+ 75%) or highly-purified inhibin (+ 64%) in a dose- and time-dependent manner. This unexpected action of bFF on GnRH-induced LH release was abolished in the presence of 5 μl specific anti-inhibin serum, confirming that the response was indeed mediated by inhibin. Furthermore, neither oestradiol-17β (1 pmol/l–10 nmol/l) nor monomeric α-subunit of bovine inhibin (2·5–40 ng/ml) significantly affected basal or GnRH-induced release of LH. These in-vitro findings for the ewe lend support to a number of recent in-vivo observations and indicate that, in addition to its well-documented suppressive effect on the synthesis and secretion of FSH, inhibin may actually facilitate LH release in this species, in marked contrast to its action in the rat. Journal of Endocrinology (1990) 127, 149–159

Variation in hypothalamic gonadotrophin-releasing hormone content, plasma and pituitary LH, and in-vitro testosterone release in a long-distance migratory bird, the garden warbler (Sylvia borin), under constant photoperiods

1991 ◽  
Vol 128 (3) ◽  
pp. 339-345 ◽  
Author(s):  
C. K. Bluhm ◽  
H. Schwabl ◽  
I. Schwabl ◽  
A. Perera ◽  
B. K. Follett ◽  
...  
Keyword(s):  
Body Mass ◽  
In Vitro Release ◽  
Gradual Change ◽  
Long Distance ◽  
Garden Warbler ◽  
Releasing Hormone ◽  
Testicular Mass ◽  
Gonadotrophin Releasing Hormone ◽  
Sylvia Borin

ABSTRACT Changes in concentrations of hypothalamic gonadotrophin-releasing hormone (GnRH), pituitary and plasma LH, testicular mass, in-vitro release of testosterone, body mass and migratory activity were measured in male garden warblers (Sylvia borin) kept from November to June under a constant photoperiod of 12·8 h. Under such conditions garden warblers gradually change from the photorefractory to the photosensitive state and gonadal recrudescence then occurs. Hypothalamic GnRH content was low from December to March, but increased in April to reach the highest levels in June. The spontaneous increase in GnRH was paralleled by increases in pituitary LH content, testicular mass and in-vitro testosterone release. Body mass decreased 1 month and nocturnal activity 2 months before the spontaneous increase in GnRH. Ovine LH increased in-vitro testosterone release over basal release at all times. The results suggest that in garden warblers (1) changes in hypothalamic GnRH content can occur under constant photoperiodic condition, (2) the gradual change from the photorefractory to the photosensitive state is not characterized by a gradual increase in hypothalamic content of GnRH (cf. starlings), and (3) Leydig cells are capable of testosterone release even during the photorefractory state. Journal of Endocrinology (1991) 128, 339–345

A gonadotrophin-releasing hormone (GnRH) antagonist inhibits GnRH- but not LH-induced meiosis in follicle-enclosed rat oocytes in vitro

1982 ◽  
Vol 101 (2) ◽  
pp. 264-267 ◽  
Author(s):  
C. Ekholm ◽  
T. Hillensjö ◽  
W. J. Le Maire ◽  
C. Magnusson ◽  
C. S. Sheela Rani
Keyword(s):  
Gnrh Agonist ◽  
Gnrh Antagonist ◽  
Similar Response ◽  
Releasing Hormone ◽  
Lactate Accumulation ◽  
Receptor Sites ◽  
Gonadotrophin Releasing Hormone ◽  
Stimulation Of

Abstract. Previous studies have shown that gonadotrophin-releasing hormone (GnRH) can induce resumption of meiosis in follicle-enclosed rat oocytes. In the present study a GnRH antagonistic analogue ([d-pGlul, d-Phe2,-d-Trp3,6]LRF) was found to effectively abolish the stimulatory effect of a GnRH agonist upon resumption of meiosis and lactate accumulation in isolated pre-ovulatory rat follicles but the have no effect on LH stimulation of these parameters. It is concluded that although LH and GnRH can evoke a similar response they act through separate receptor sites and that it is unlikely that GnRH mediates the effect of LH on meiosis or glycolysis.

Effect of chronic exposure to a gonadotrophin-releasing hormone agonist on in vitro responsiveness of ovine pituitary cells to inhibin, activin and oestradiol

1994 ◽  
Vol 140 (3) ◽  
pp. 483-493 ◽  
Author(s):  
S Muttukrishna ◽  
P G Knight
Keyword(s):  
Gnrh Agonist ◽  
Inhibitory Effect ◽  
Pituitary Cells ◽  
Cell Content ◽  
Releasing Hormone ◽  
Basal Release ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone

Abstract To investigate the extent to which the direct actions of inhibin, activin and oestradiol on pituitary output of FSH and LH are dependent on the presence of functional gonadotrophin-releasing hormone (GnRH) receptors, we have compared the effects of these agents on cultured ovine pituitary cells derived from control and GnRH agonist-suppressed ewes. Chronic treatment with GnRH agonist reduced plasma LH and FSH levels (P<0·01) and abolished GnRH-induced release of LH and FSH both in vivo and in vitro. As expected, basal LH release and LH cell content in vitro were drastically reduced in GnRH agonist-suppressed cells (P<0·001). However, basal FSH release and FSH cell content were approximately twofold higher than in control cells (P<0·001). Irrespective of whether the cells had been desensitized to GnRH, inhibin and oestradiol were both found to suppress basal FSH release and FSH cell content in a dose-dependent fashion (P<0·001). Although inhibin had no effect on basal release of LH from control cells, it markedly enhanced GnRH-induced release (P<0·001). In contrast, inhibin increased (P<0·001) basal LH release from GnRH agonist-suppressed cells (which were unresponsive to the GnRH challenge). Inhibin had no overall effect on total LH content/well for either control or GnRH agonist-suppressed cells. Treatment with oestradiol, on the other hand, reduced total LH content/well, an effect which was more pronounced with GnRH agonist-suppressed cells (−44%; P<0·001) than with control cells (−14%, P<0·01). Whereas in control cells activin had no significant effect on any aspect of FSH production examined, in GnRH agonist-treated cells activin enhanced basal FSH release, residual cell content and total FSH content/well (P<0·001). Altering GnRH receptor status also modified the LH response to activin. With control cells activin increased basal release (P<0·001), decreased GnRH-induced release (P<0·001) and increased total LH content/well (P<0·001). With GnRH agonist-treated cells, however, activin had a uniform inhibitory effect on each aspect of LH production examined (P<0·001 in each case). It was concluded that desensitization of ovine gonadotrophs to GnRH by chronic agonist treatment results in a paradoxical enhancement of FSH output in vitro but has little effect on the responsiveness of the cells (in terms of gonadotrophin release and content) to either inhibin or oestradiol. In contrast, GnRH agonist treatment leads to qualitative changes in cellular reponsiveness to activin. Journal of Endocrinology (1994) 140, 483–493

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