PITUITARY SENSITIVITY TO GONADOTROPHIN RELEASING HORMONE AFTER HYPERPROLACTINAEMIA INDUCED WITH NEUROLEPTICS AND DOMPERIDONE IN THE RAT

1981 ◽  
Vol 91 (3) ◽  
pp. 439-446 ◽  
Author(s):  
D. A. CARTER ◽  
S. A. WHITEHEAD

The effect of hyperprolactinaemia induced by dopamine-antagonist drugs on pituitary responsiveness to gonadotrophin releasing hormone (Gn-RH) and on plasma LH levels has been investigated in intact and ovariectomized rats. The animals were pretreated with haloperidol, pimozide or domperidone and the sensitivity of isolated pituitary glands to pulses of Gn-RH were tested using a perifusion system. Trunk blood, collected at the time of killing, was assayed for plasma LH and prolactin. In addition, a direct effect of the drugs on pituitary responsiveness to Gn-RH was investigated by perifusing pituitary glands taken from untreated, pro-oestrous rats in medium containing the dopamine antagonists. The pituitary responsiveness was significantly impaired in intact rats after treatment with each of the drugs whereas no effect was observed in pretreated ovariectomized rats. None of the drug treatments altered levels of circulating LH. High concentrations of the drugs present in the perifusion medium also inhibited pituitary responsiveness although it is not known whether the concentrations of the drugs present in the pretreated animals would exert a similar effect. The results suggest that short-term hyperprolactinaemia impairs pituitary responsiveness through a modulation of ovarian steroid secretion and that Gn-RH release is not altered. Treatment with domperidone exhibited similar effects on the parameters measured here to those caused by the two neuroleptics, indicating that this novel anti-dopaminergic drug is acting in a similar manner.

1976 ◽  
Vol 68 (1) ◽  
pp. 127-136 ◽  
Author(s):  
MARTA E. APFELBAUM ◽  
S. TALEISNIK

SUMMARY The release and synthesis of LH and FSH were studied in adenohypophyses from ovariectomized rats incubated for a period of 4 h in flasks containing 1 ml Eagle's medium. One hemipituitary was used as the experimental gland and the other half served as a control. Glands from ovariectomized untreated animals showed a spontaneous release of LH and FSH and the amount of hormones released (per mg gland) by both the hemipituitaries was not significantly different. Also the content of the hormones at the end of the incubation period was similar in both halves. Gonadotrophin-releasing hormone (Gn-RH) added to the incubation medium stimulated the release of LH and FSH. A dose–response relationship was obtained between doses of 0·51 and 8·00 ng/ml medium. Although lower doses were required to increase the release of LH, the amount of FSH released was higher when expressed as a percentage of gland content. Pituitary glands from ovariectomized rats treated with 5 μg oestradiol benzoate 24 h before being killed showed an increase in sensitivity to Gn-RH, but the response decreased when oestrogen was injected 2 h before death. Also the addition of oestradiol-17β to the incubation medium inhibited LH and FSH release induced by Gn-RH. Gonadotrophin-releasing hormone increased the spontaneous synthesis of LH and FSH observed in the incubated pituitaries. This effect of Gn-RH was stimulated by the injection of oestrogen into the donor animals whereas administration of oestrogen into the medium enhanced the synthesis of LH and partially inhibited that of FSH. These results provide evidence for a dual effect of oestrogen on the release of LH and FSH induced by Gn-RH. They also show that synthesis of gonadotrophic hormones was favoured by oestrogen or by increased gonadotrophin release.


1994 ◽  
Vol 141 (2) ◽  
pp. 317-324 ◽  
Author(s):  
G B Thomas ◽  
A S McNeilly ◽  
F Gibson ◽  
A N Brooks

Abstract In order to investigate the regulation of the hypothalamo-pituitary-gonadal axis during fetal development, sheep fetuses at day 70 of gestation were implanted subcutaneously with a biodegradable implant containing the longacting gonadotrophin-releasing hormone (GnRH) agonist, buserelin. The treatment of fetuses with a GnRH agonist throughout the last half of gestation (term=145 days) abolished the increase in plasma LH concentrations that was seen in 2-day-old control lambs in response to an injection of GnRH. This attenuated response was associated with corresponding reductions in the pituitary content of LH and FSH. Immunolocalization studies revealed that pituitary glands from newborn lambs implanted with a GnRH agonist during fetal development were devoid of immunopositive LH- and FSH-containing cells. At birth the testicular weights of GnRH agonist-treated ram lambs were significantly decreased by 40% when compared with controls. This was associated with a 45% reduction in the total number of Sertoli cells per testis. In newborn ewe lambs GnRH agonist treatment had no effect on ovarian weight or on the morphological appearance of the ovaries. GnRH agonist treatment had no effect on the plasma concentrations of progesterone and oestrone in the maternal circulation or on the length of gestation. These results show (1) that GnRH positively regulates the synthesis and secretion of gonadotrophins in the fetus, (2) that reduced fetal gonadotrophic support during the last half of gestation results in a reduction in testicular growth, and (3) that fetal gonadotrophins do not affect maternal steroid secretion. Journal of Endocrinology (1994) 141, 317–324


1991 ◽  
Vol 125 (6) ◽  
pp. 581-589 ◽  
Author(s):  
Charla M. Blacker ◽  
Khalid M. Ataya ◽  
Ruth T. Savoy-Moore ◽  
Marappa G. Subramanian ◽  
Milton G. Mutchnick ◽  
...  

Abstract. To evaluate the effects of a gonadotropin-releasing hormone agonist on non-reproductive systems, we administered [D-Leu 6, Des-gly 10]-GnRH ethylamide (leuprolide; 5 μg/day) for 21 days to female Sprague-Dawley rats. In Experiment 1, continuous infusion (Alzet minipumps sc) was compared to injection. Increased thymus and body weights and decreased estradiol and uterine weights were noted for both administration methods. Spleen weight increased only in rats treated by continuous infusion. Ovary, kidney and liver weights did not change. Only leuprolide-injected rats had elevated LH with decreased corticosterone and ACTH levels, possibly related to the injection process. Glucose, insulin, progesterone, FSH and corticosterone/ACTH were not different. In Experiment 2, intact and ovariectomized rats were implanted with minipumps delivering leuprolide or 0.9% NaCl. Body and thymus weights increased, whereas uterine weight and estradiol declined in both leuprolide-treated and ovariectomized rats. No synergism between leuprolide and ovariectomy was noted. Thymosin α1, but not thymosin β4, increased in leuprolide-treated ovariectomized rats. Peripheral white blood cell count was elevated in leuprolide-treated intact rats and ovariectomized rats. In bone marrow, non-nucleated cell count declined in leuprolide-treated intact rats, contributing to the decreased total cell count in this group. Nucleated cell count was unaffected. Therefore, thymus weight gain was accompanied only in some cases by functional changes. Our results demonstrate that leuprolide affects non-reproductive systems, in a similar manner to ovariectomy. We suggest that such alterations may be due to the hypoestrogenic environment produced by leuprolide.


1981 ◽  
Vol 88 (3) ◽  
pp. 375-379
Author(s):  
J. DULLAART

Hemipituitary glands of immature female rats, aged 10, 15, 20, 25, 30 and 35 days and either ovariectomized or sham-operated 5 days earlier, were incubated for 2 h in vitro with or without LH releasing hormone. Concentrations of LH and FSH were determined at the end of the incubations in the incubation media and in the hemipituitary glands, and also in the sera collected at the beginning of the incubation experiments. Results showed that in many instances gonadotrophin release was higher after incubation of glands of ovariectomized rats than with glands of control animals. However, these effects of ovariectomy were much smaller than those observed in vivo and were generally absent in rats of less than 20 days of age. It was concluded that ovariectomy may change the secretory characteristics of the gonadotrophic cells of immature rats but that such changes were largely restricted to immature rats older than 20 days.


1982 ◽  
Vol 94 (1) ◽  
pp. 11-20 ◽  
Author(s):  
J. de Koning ◽  
A. M. I. Tijssen ◽  
J. A. M. J. van Dieten ◽  
G. P. van Rees

Continuous exposure of hemi-pituitary glands from intact female rats to LH releasing hormone (LH-RH) in vitro displayed three phases in the pattern of LH release: during the first hour release of LH was low (first phase response), then it increased to a higher level during the second hour and remained constant during the next 2 h (second phase response), after which there was a refractoriness of LH release (third phase response). The initial phase response of pituitary glands from intact rats was blocked by EGTA (a Ca2+ chelator) but there was a small but significant increase in the rate of LH release during the second phase response. This increase could be prevented by inhibition of protein synthesis by cycloheximide. Cycloheximide and EGTA did not affect basal release of LH by glands from intact rats, neither did EGTA affect the high basal release of LH by glands from ovariectomized rats. However, the LH-RH-induced release of LH from pituitary glands of ovariectomized rats, which did not show the initial phase of low LH release, was completely suppressed by EGTA throughout a 4-h incubation period. The pattern of LH release stimulated by the combination of N6-monobutyryl cyclic AMP and theophylline (mbcAMP/theophylline) showed an initial phase of low LH release lasting 4 h after which it increased. The magnitude of the effect was small compared with the action of LH-RH. As it did with LH-RH, EGTA completely blocked the initial response, but allowed a small increase in the rate of LH release thereafter; this increase could also be blocked by inhibition of protein synthesis. Addition of EGTA to media during pretreatment of pituitary glands from intact rats with either LH-RH or mbcAMP/theophylline did not impair the facilitatory effect of these secretagogues on the responsiveness of the glands to subsequent exposure to LH-RH and cycloheximide and normal Ca2+ levels. The restoration of Ca2+ levels after withdrawal neither affected basal nor LH-RH-induced release of LH. Exclusion of Ca2+ from the media during a 6-h incubation of pituitary glands from intact rats with LH-RH prevented the glands from becoming refractory to subsequent stimulation by LH-RH, which occurs when normal Ca2+ concentrations are present. The results suggested that extracellular Ca2+ is obligatory for LH release and the induction of refractoriness by LH-RH. In contrast, that part of the action of LH-RH which is cyclic AMP-mediated and protein synthesis-dependent is not affected by withdrawal of extracellular Ca2+.


1989 ◽  
Vol 121 (2) ◽  
pp. 325-330 ◽  
Author(s):  
S. M. Rhind ◽  
G. B. Martin ◽  
S. McMillen ◽  
C. G. Tsonis ◽  
A. S. McNeilly

ABSTRACT The effect of level of food intake on LH and FSH profiles and pituitary sensitivity to gonadotrophin-releasing hormone (GnRH) was investigated in two groups of 12 ovariectomized ewes. Ewes with a high intake (group H) had a mean daily intake (± s.e.m.) of 1·99 ± 0·075 kg dry matter (DM)/head per day while ewes with a moderate intake (group M) consumed a mean of 1·02 ± 0·021 kg DM/head per day. Ovaries were surgically removed from six ewes of each group on day 11 of the luteal phase and from the remainder 30 h after an injection of 100 μg prostaglandin analogue given on day 11 to induce luteolysis. During both the luteal phase and the follicular phase, mean LH and FSH concentrations and LH pulse frequencies and amplitudes were unaffected by the level of intake but mean plasma prolactin concentrations were higher (P < 0·05) in group H than in group M ewes in the follicular phase. Mean LH and FSH concentrations at day 2 after ovariectomy were unaffected by treatment while mean prolactin concentrations were higher (P < 0·05) in group H than in group M ewes. At day 7 after ovariectomy, mean LH and FSH concentrations were lower (P < 0·05) in group H than in group M ewes although mean LH pulse frequencies and pulse amplitudes were not significantly affected by the level of intake at either time. The level of food intake and the stage of the oestrous cycle at the time of ovariectomy did not affect the amount of LH released in response to a bolus injection of GnRH (10 μg, i.v.) but the FSH response was significantly (P < 0·05) greater in group M than in group H ewes. It is concluded that the pituitary glands of ovariectomized ewes with moderate levels of intake are more responsive to GnRH than those of ewes with a high intake and that hypothalamic activity and GnRH secretion are not affected by the level of food intake. Journal of Endocrinology (1989) 121, 325–330


1991 ◽  
Vol 128 (3) ◽  
pp. 411-418
Author(s):  
T. R. Koiter ◽  
G. C. J. van der Schaaf-Verdonk ◽  
G. A. Schuiling

ABSTRACT We investigated whether the increase in the gonadotrophin response to gonadotrophin-releasing hormone (GnRH) during the last days of pregnancy and the occurrence of parturition on day 22 of pregnancy in rats are due to the increase in the plasma concentrations of oestradiol-17β after luteolysis, which occurs around day 20. In a first series of experiments we studied the effects of s.c. implantation of two capsules containing oestradiol on basal and GnRH-stimulated secretion of LH and FSH before and after luteolysis. Before luteolysis, ovariectomy increased basal LH and FSH; oestradiol treatment prevented this increase partly (FSH) or completely (LH). Ovariectomy also lowered the LH response to the infusion of GnRH (100 ng/h). Oestradiol treatment, on the other hand, increased the LH and FSH responses of both intact and ovariectomized rats above the level in intact non-treated control rats. After luteolysis, ovariectomy increased basal FSH only. Treatment with oestradiol did not prevent the increase in basal FSH and ovariectomy diminished the LH response to GnRH infusion. Oestradiol treatment maintained the LH response in ovariectomized rats at the control level and increased the FSH responses of both intact and ovariectomized rats to a higher level than in control rats. Furthermore, the LH and FSH responses of the oestradiol-treated groups of intact and ovariectomized rats were higher after luteolysis than before. In a second series of experiments two capsules containing progesterone were s.c. implanted before or after luteolysis. Progesterone treatment suppressed the plasma concentration of oestradiol and the gonadotrophin responses to infusion of GnRH on the expected day of parturition in both groups of rats. Parturition was delayed only in the rats in which progesterone treatment had started before luteolysis. It was concluded that throughout pregnancy ovarian factors suppress basal FSH and that the increase in responsiveness to GnRH after luteolysis is due partly to an increase in oestradiol production and partly to an ovarian factor which augments the action of oestradiol. Furthermore, normal delivery does not require high plasma concentrations of oestradiol during the last day of pregnancy. Journal of Endocrinology (1991) 128, 411–418


1989 ◽  
Vol 121 (2) ◽  
pp. 239-247 ◽  
Author(s):  
R. De Leeuw ◽  
H. R. Habibi ◽  
C. S. Nahorniak ◽  
R. E. Peter

ABSTRACT In goldfish, dopamine acts as an endogenous inhibitor of basal and gonadotrophin-releasing hormone (GnRH)-stimulated gonadotrophin release. The purpose of the present study was to investigate the effects of dopamine on the pituitary GnRH receptors in vivo and in vitro in goldfish. The goldfish pituitary contains two classes of GnRH-binding sites, a high-affinity/low-capacity site and a low-affinity/high-capacity site. Injection of domperidone, a dopamine antagonist, resulted in a dose- and time-related increase in capacity of both the high- and low-affinity GnRH-binding sites; apomorphine, a dopamine agonist, completely reversed this effect. The effects on GnRH receptor capacity correlated very closely with changes in serum gonadotrophin concentrations. Domperidone was generally without effect on GnRH-binding affinity; however, a small but significant decrease in affinity was observed for the low- affinity binding site at 18 h after injection of the highest dose of domperidone used (40 μmol/kg body weight). Treatment with apomorphine of goldfish pituitary fragments in a perifusion system caused a decrease in the capacity of both the high- and low-affinity GnRH-binding sites without affecting binding affinity; domperidone reversed this effect. It is concluded that the dopaminergic inhibition of basal and GnRH-stimulated gonadotrophin release in goldfish might, in part, be the result of a down-regulation of the pituitary GnRH receptors; this effect of dopamine can be achieved by a direct action at the pituitary level. Journal of Endocrinology (1989) 121, 239–247


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