Divergent effects of gonadotrophin-releasing hormone (GnRH) analogue and authentic GnRH on the anterior pituitary gland of rats with restricted feeding

1995 ◽  
Vol 145 (3) ◽  
pp. 501-511 ◽  
Author(s):  
K Goto ◽  
F Kotsuji ◽  
T Tominaga

Abstract The effects of gonadotrophin-releasing hormone analogue (GnRHa; buserelin) on the pituitary function and morphology of food-restricted rats were compared with those of authentic GnRH. After adult female rats had been restricted to 10 g food/day for 60 days, various doses of GnRHa (10 ng, 100 ng and 1 μg) or GnRH (10 μg) were administered either daily for 7 days or twice a week for 4 weeks from day 61 of the period of underfeeding. Underfeeding brought about a decrease in the pituitary gonadotrophin content, serum levels of gonadotrophins and oestradiol, and the number and size of both LH- and FSH-positive pituitary cells. Daily and/or twice-weekly administration of authentic GnRH to underfed rats produced an increase in pituitary and serum gonadotrophin levels and the number and size of both LH- and FSH-positive pituitary cells. The administration of GnRHa daily for 7 days increased serum gonadotrophin levels, while it produced a reduction in the pituitary gonadotrophin content and number and size of both LH- and FSH-positive pituitary cells in a dose-dependent manner. Twice-weekly administration of GnRHa also produced an elevation of serum gonadotrophin levels and reduction of pituitary gonadotrophin content, although it did not affect the numbers and areas of LH- and FSH-positive pituitary cells. A GnRH loading test performed after the GnRHa treatment showed that the GnRHa treatment performed in this study did not produce down-regulation of the GnRH receptor. Thus, it can be concluded that the gonadotrophin-synthesizing activity of GnRHa is weaker than that of authentic GnRH, or that GnRHa may preferentially exert gonadotrophin-releasing activity rather than gonadotrophin-synthesizing activity in the anterior pituitary of underfed rats. Journal of Endocrinology (1995) 145, 501–511

1992 ◽  
Vol 134 (2) ◽  
pp. 177-NP ◽  
Author(s):  
F. Kotsuji ◽  
K. Hosokawa ◽  
T. Tominaga

ABSTRACT To investigate the influence of weight reduction on pituitary function and its modulation by gonadotrophin-releasing hormone (GnRH), female rats were restricted to 10 g food/day for 60 days. GnRH (5 μg) or saline (0·2 ml) were administered daily between days 31 and 60 of the period of underfeeding. Underfeeding brought about a decrease in the pituitary gonadotrophin content, serum levels of gonadotrophins and oestradiol, and the number and size of both LH- and FSH-positive pituitary cells. The administration of GnRH to underfed rats produced an increase in the pituitary and serum gonadotrophin levels and the number and size of both LH- and FSH-positive pituitary cells. These observations suggest that underfeeding and/or weight loss diminish the number and activity of the pituitary gonadotrophs, and that daily administration of GnRH both increases the number of gonadotrophs and augments their activity. Journal of Endocrinology (1992) 134, 177–182


1992 ◽  
Vol 132 (3) ◽  
pp. 395-NP ◽  
Author(s):  
F. Kotsuji ◽  
K. Hosokawa ◽  
T. Tominaga

ABSTRACT Gonadotrophin-releasing hormone (GnRH) has been shown to regulate the synthesis and release of gonadotrophins acutely, yet few studies have investigated the chronic effects of this agent on pituitary gonadotrophins. In the present study we determined the effect of chronic administration of GnRH on the female rat pituitary gland. Rats of 8 weeks of age were injected s.c. with various doses of GnRH daily for 30 days. After completion of the GnRH treatment, treated rats and age-matched controls were killed by decapitation at 09.00 h on the first day of dioestrus, as determined from vaginal smears. Treatment with 10 ng–10 μg GnRH/day increased pituitary contents of FSH and LH in a dose-dependent manner. The change in FSH content was much greater than that of LH content. The pituitary FSH content of rats treated with 40 μg GnRH was significantly less than that of rats treated with 10 μg GnRH. There was a marked increase in the number of cells which stained positively for FSH (266%) and LH (28%) in the anterior pituitary of rats given 10 μg GnRH, but there was no demonstrable change in the areas of single cells stained positively for FSH and LH. Serum levels of LH, FSH and oestradiol were not affected by the GnRH treatment. These data indicate that chronic administration of GnRH is capable of increasing the pituitary gonadotrophin content and numbers of FSH and/or LH-stained cells and that FSH cells are affected more than LH cells by the GnRH treatment. The increase in pituitary gonadotrophin content, however, does not necessarily produce an increase in circulating levels of gonadotrophins. Journal of Endocrinology (1992) 132, 395–400


1985 ◽  
Vol 249 (4) ◽  
pp. E392-E397
Author(s):  
W. S. Evans ◽  
T. H. Brannagan ◽  
E. R. Limber ◽  
M. J. Cronin ◽  
A. D. Rogol ◽  
...  

The effects of forskolin, an agent which increases intracellular levels of cAMP, on basal luteinizing hormone (LH) and growth hormone (GH) release and on gonadotropin-releasing hormone (GnRH)-stimulated LH release were documented. Continuously perifused dispersed anterior pituitary cells from female rats at random stages of the estrous cycle were used. Secretory rates of both LH and GH increased in a concentration-dependent manner in response to a 1-h challenge with 0.03, 0.1, 0.3, 1, or 3 microM forskolin. In response to 0.3 microM forskolin, maximum GH release was achieved within 15-20 min, after which secretion decreased. In contrast, LH release increased gradually, became maximal at 1.5-2 h, and remained constant until the forskolin was withdrawn. Cells exposed to 10 nM GnRH for 4 h exhibited a biphasic release of LH with the interphase nadir occurring at 30 min. The second phase of LH release was enhanced by simultaneous addition of forskolin with the GnRH. Whereas second phase release did not increase further, exposure of the cells to forskolin for 60 or 120 min before GnRH resulted in increased first-phase LH release. We suggest that, whereas our data are consistent with a role for cAMP in mediating the acute release of GH, cAMP may be involved in the process through which nonimmediately releasable LH becomes available for release.


1990 ◽  
Vol 127 (1) ◽  
pp. 149-159 ◽  
Author(s):  
S. Muttukrishna ◽  
P. G. Knight

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


1981 ◽  
Vol 241 (4) ◽  
pp. E298-E304
Author(s):  
G. Snyder ◽  
Z. Naor ◽  
C. P. Fawcett ◽  
S. M. McCann

Anterior pituitary cells from 15-day female rats were separated by unit gravity sedimentation into four populations (designated regions I-IV) based on the profile of cell distribution and the resulting content of radioimmunoassayable (RIA) hormones. The cells in regions II and IV released thyrotropin (TSH) in response to thyrotropin-releasing hormone (TRH, 5 ng/ml); however, those in region IV released only approximately 5% of their RIA content, whereas those in region II released approximately 26% in response to the same stimulus. Concomitant elevation of cAMP and of cGMP occurred in region II cells but only cGMP was elevated in region IV cells. Mammotrophs were localized in region III. They responded to TRH by releasing prolactin (PRL) and exhibiting increased cAMP content. These data provide support for the existence of two functionally distinct populations of thyrotrophs in 15-day-old female rats. The data also imply that cAMP is involved in TRH induced PRL release, whereas cGMP is involved in TRH-induced TSH release.


1983 ◽  
Vol 98 (3) ◽  
pp. 411-421 ◽  
Author(s):  
R. P. McIntosh ◽  
J. E. A. McIntosh

The effects were studied of varying the frequency, width and amplitude of pulses of gonadotrophin releasing hormone (GnRH) on the release of LH from anterior pituitary cells. Dispersed sheep cells supported in Sephadex were perifused with medium for 10 h and stimulated with different constant pulse patterns of GnRH. The timing of release of LH was measured by radioimmunoassay of the effluent fractions. Pulses of GnRH ranging in duration from 2 min every 8 min to 16 min every 128 min, and in concentration from 1·7 pmol/l to 250 nmol/l were applied to the cells, as well as continuous stimulation. Comparisons of differences between LH release patterns among samples of the same preparation of cells were used to demonstrate the effects of different GnRH stimulatory regimes. It was concluded that (1) the frequency of GnRH stimulation was important to the nature of LH release (periods shorter than about 16 min between pulses reduced LH output and caused faster desensitization of response), (2) the pulse width of GnRH input was important (the rising edge of the pulse produced greater LH output per unit of GnRH input than did continued application of GnRH within a pulse and wider pulses combined with shorter periods reduced LH output) and (3) over a threshold value of 5–10 nmol GnRH/1 pulse amplitude had little further influence on LH output or rate of desensitization in dispersed cells. These findings reinforce the hypothesis that the rising edge of the GnRH pulse is the major stimulant to LH release.


1982 ◽  
Vol 99 (1) ◽  
pp. 44-49 ◽  
Author(s):  
L. W. Eddie ◽  
H. W. G. Baker ◽  
R. E. Higginson ◽  
B. Hudson

Abstract. Primary monolayer cultures of adult male rat anterior pituitary cells secreted both LH and FSH in a biphasic manner when incubated with gonadotrophin releasing hormone (GnRH). The peaks of secretion of LH and FSH were coincident; the first occurred between 15 and 30 min and the second between 1 and 3 h after the addition of GnRH. Approximately 20% of the total amount of gonadotrophins secreted in the 6 h treatment with GnRH was contained in the first peak. Inhibitors of the secretion of gonadotrophins affected LH and FSH secretion differently. Inhibin suppressed the secretion of FSH to a greater extent than that of LH, whereas testosterone and cycloheximide had a greater effect on LH. Neither phase of secretion of LH or FSH was reduced preferentially by inhibin or testosterone but the greater effect of cycloheximide was on the second phase of secretion.


2010 ◽  
Vol 298 (3) ◽  
pp. E644-E651 ◽  
Author(s):  
Hana Zemkova ◽  
Marek Kucka ◽  
Shuo Li ◽  
Arturo E. Gonzalez-Iglesias ◽  
Melanija Tomic ◽  
...  

Anterior pituitary cells express cation-conducting P2X receptor channels (P2XRs), but their molecular identity, electrophysiological properties, cell-specific expression pattern, and physiological roles have been only partially characterized. In this study, we show by quantitative RT-PCR that mRNA transcripts for the P2X4 subunit are the most abundant in rat anterior pituitary tissue and confirm the P2X4R protein expression by Western blot analysis. Single-cell patch-clamp recordings show that extracellular ATP induced an inward depolarizing current in a majority of thyrotropin-releasing hormone-responsive pituitary cells, which resembled the current profile generated by recombinant P2X4R. The channels were activated and desensitized in a dose-dependent manner and deactivated rapidly. Activation of these channels led to stimulation of electrical activity and promotion of voltage-gated and voltage-insensitive Ca2+ influx. In the presence of ivermectin, a specific allosteric modulator of P2X4Rs, there was an approximately fourfold increase in the maximum amplitude of the ATP-induced inward current, accompanied by an increase in the sensitivity of receptors for ATP, slowed deactivation of receptors, and enhanced ATP-induced prolactin release. These results indicate that thyrotropin-releasing hormone-responsive cells, including lactotrophs, express homomeric and/or heteromeric P2X4Rs, which facilitate Ca2+ influx and hormone secretion.


2020 ◽  
Vol 32 (2) ◽  
pp. 205
Author(s):  
M. Kaps ◽  
C. Gautier ◽  
C. Cardoso Okada ◽  
J. Kuhl ◽  
J. Aurich ◽  
...  

Oestrus behaviour in mares can contribute to problems in their handleability and reduced performance in equestrian sports. Therefore, methods of transient suppression of oestrous cyclicity in mares are of interest. The aim of our study was to determine whether treatment of mares with slow-release implants containing the gonadotrophin-releasing hormone (GnRH) analogue deslorelin downregulates pituitary GnRH receptors and reduces ovarian function and oestrous behaviour. Shetland mares (age=11.0±1.4 years; bodyweight=185.5±7kg) were oestrous synchronised with two injections of the prostaglandin F2α analogue luprostiol (3.725mg) at an interval of 12 days. One day after the second injection (Day 0), mares were randomly assigned to three groups: slow-release implant with 9.4mg of deslorelin (Suprelorin, Virbac; group D1; n=6), implant with 4.7mg of deslorelin (group D2; n=5), and intramuscular injection of 1.25mg of short-acting deslorelin (control, group C; n=5). Collection of blood samples for analysis of progesterone, LH, and anti-Müllerian hormone (AMH) using established and validated enzyme immunoassays (Scarlet et al. 2018 Theriogenology 117, 72-77), testing for oestrus-like behaviour with a Shetland stallion, and ultrasonography of the genital tract were performed at 2-day intervals until Day 10 after treatment and at 5-day intervals from there. On Days 10 and 45 after treatment, LH stimulation tests with the GnRH agonist buserelin (4µg IV) were performed. Data were normally distributed; differences among groups were analysed using analysis of variance and subsequent Tukey test. Values are means±s.e.m. In all mares without a corpus luteum on Day 0 (progesterone &lt;1ngmL−1; one mare in group D1 and two in group C), ovulation was detected within 9 days after deslorelin treatment. These ovulations were classified as deslorelin induced, whereas ovulations after Day 10 were classified as spontaneous ovulations. The mean interval from deslorelin until the first spontaneous ovulation was 62.0±8.6, 44.2±14.1, and 22.2±3.1 days in groups D1, D2, and C (P&lt;0.05), respectively. Subsequent oestrous cycles were regular. Oestrus-like behaviour until day 50 was reduced in groups D1 (2.0±0.9 days) and D2 (2.4±1.3 days) compared with group C (6.4±1.2 days; P&lt;0.05). Concentration of plasma LH and AMH decreased in group D1 (P&lt;0.05) but not in groups D2 and C. The GnRH stimulation test on Day 10 resulted in an increase (P&lt;0.001) in plasma LH concentration in group C but not in groups D1 and D2 (treatment×time P&lt;0.05). On Day 45, LH concentration increased in all mares in response to buserelin (NS among groups). Within 100 days of treatment, LH concentrations but not AMH concentrations in mares of group D1 returned to baseline. In conclusion, deslorelin slow-release implants transiently suppress ovarian function and oestrus behaviour in mares. Spontaneous ovulation is delayed in a dose-dependent manner. A decrease in AMH concentration suggests inhibitory effects of deslorelin on small antral follicles. Long-term effects on follicular dynamics and fertility in larger horses also need to be assessed.


1986 ◽  
Vol 111 (3) ◽  
pp. 312-320 ◽  
Author(s):  
G. Emons ◽  
O. Ortmann ◽  
U. Fingscheidt ◽  
P. Ball ◽  
R. Knuppen

Abstract. Dispersed pituitary cells from adult female rats were preincubated for different time periods (0– 12 h) in the absence or presence of 10−9 moestradiol (E2) or 4-hydroxyoestradiol (4-OHE2). Then the media were changed and the cells incubated for 4 h with either vehicle, or E2, or 4-OHE2 and additionally with different concentrations (10−11– 10−7 m) of gonadotrophin-releasing hormone (GnRH). Treatment of pituitary cells with E2 for 4 h (i.e. no preincubation with E2) significantly decreased the LH-response to GnRH at concentrations ≥ 10−10 m of the decapeptide. During a transition time of approximately 10 h (i.e. in cultures preincubated with E2 or vehicle for 2, 4, 6 or 8 h and then coincubated with E2 or vehicle and GnRH for 4 h) no differences between E2-and vehicle-treated cultures were observed. After 14 and 16 h of E2-treatment (i.e. 10 or 12 h preincubation and 4 h coincubation with GnRH) the LH-responses to GnRH in these cultures were significantly higher than in the respective controls. A nearly identical reaction pattern was observed when 4-OHE2 was used instead of E2. In a second series of experiments dispersed rat pituitary cells were suspended in a carrier gel and continuously perifused with medium, using small chromatography columns. When these cells were exposed for 4 min to 10−9 m GnRH at 60 or 48 min intervals, they reacted with reproducible pulsatile LH-discharges during at least 6 subsequent stimuli with the decapeptide. When E2 (10−9 m) was added to the perifusion medium, the LH-responses to GnRH were significantly reduced, starting 36 min after the onset of E2-treatment. These data indicate: 1) In the rat, the negative oestrogen effect is at least in part directly mediated at the pituitary level. 2) The sensitizing effect of oestrogens on rat gonadotrophs to GnRH is significant already after 14 to 16 h. 3) E2 and the catecholoestrogen 4-OHE2 have the same effects in this system. 4) The negative E2-effect on GnRH-induced LH-release is significant after only 36 min, a finding bringing up the question of a non-genomic mechanism.


Sign in / Sign up

Export Citation Format

Share Document