Flurothyl-induced convulsions delay the onset of sexual maturation in the female rat

1982 ◽  
Vol 95 (1) ◽  
pp. 37-41 ◽  
Author(s):  
M. Wilkinson ◽  
R. Bhanot ◽  
J. A. Pincock ◽  
L. Donald

We have investigated whether sexual maturation in female rats is affected by repeated flurothyl-induced convulsions. This treatment had no effect on the normal age-related increase in body weight though puberty (vaginal opening) was significantly delayed when compared with non-convulsed control rats. In an attempt to probe the mechanism of this delaying effect we observed that (1) anterior pituitary response to gonadotrophin releasing hormone in vitro was normal in terms of LH release but FSH secretion was impaired and (2) progesterone injection in oestrogen-primed convulsed rats failed to generate an ovulatory-type surge of LH or FSH. Basal serum levels and basal in-vitro secretion of LH and FSH were normal. We conclude that repeated convulsions adversely affect the hypothalamo-pituitary-gonadotrophin system of immature female rats.

1977 ◽  
Vol 74 (1) ◽  
pp. 11-21 ◽  
Author(s):  
M. WILKINSON ◽  
D. DE ZIEGLER ◽  
DANIELLE CASSARD ◽  
K. B. RUF

The effects of oestrogen priming on the sensitivity of the anterior pituitary gland to stimulation with gonadotrophin releasing hormone (GnRH) was investigated in immature female rats using a new organ culture technique. Hemipituitary glands obtained from animals primed with a single dose of oestradiol benzoate (OB; 20 μg/100 g body weight) released significantly more LH when pulsed with GnRH (4 nmol/l) than did control hemipituitary glands. This potentiating effect was detectable as early as 5 days after birth. After a second stimulation, LH secretion remained high. These results were compared with those obtained from animals treated to induce increased levels of endogenous oestrogen on day 26 of life. Thus, hemipituitary glands were obtained from animals given two injections of OB, an injection of pregnant mare serum gonadotrophin (PMSG) or a unilateral brain lesion placed in the basal hypothalamus. Pituitary tissue was stimulated as before with a pulse of GnRH. Two injections of OB enhanced the sensitivity to stimulation. Conversely, both PMSG and lesion treatment severely reduced the sensitivity to GnRH, although PMSG-treated and lesioned animals have been used as models for the study of ovulation.


1995 ◽  
Vol 145 (1) ◽  
pp. 113-119 ◽  
Author(s):  
J J Evans ◽  
S J Hurd ◽  
D R Mason

Abstract Although GnRH is believed to be the primary secretagogue for LH, oxytocin has also been shown to stimulate LH release from the anterior pituitary. We investigated the possibility that the two secretagogues interact in the modulation of LH release. Anterior pituitaries were removed from adult female rats at pro-oestrus, and tissue pieces were pre-incubated in oxytocin for 3 h prior to being stimulated with 15 min pulses of GnRH. LH output over the 1 h period from the beginning of the GnRH pulse was determined. Control incubations were carried out in the absence of oxytocin, and background secretory activities without GnRH stimulation were also determined. Tissue which was pre-exposed to oxytocin (0·012–1·25 μm) had an increased LH response to GnRH (1·25 nm). The increase was larger than the sum of the LH outputs obtained with oxytocin and GnRH separately, revealing that oxytocin synergistically enhanced LH secretion elicited by GnRH (P<0·05; ANOVA). If stimulation by GnRH was delayed for 2 h after incubation with oxytocin, an increase in LH secretion was still observed, indicating that oxytocin-induced modulation did not rapidly disappear. Oxytocin pre-incubation was observed to result in an increase of maximal GnRH-induced LH output (P<0·001; t-test), as well as an increase of intermediate responses. The LH response of the anterior pituitary to subsequent pulses of GnRH was modified by the self-priming process. The effect of oxytocin pretreatment on the response of primed tissue to GnRH was also investigated. It was found that pre-incubation in oxytocin also enhanced the LH response of primed tissue to GnRH. The study has revealed that oxytocin increases the LH output of anterior pituitary tissue in response to GnRH. The effect occurs on both GnRH-primed and unprimed tissues. The results suggest that oxytocin has the potential to regulate the dynamics of the pro-oestrous LH surge. Journal of Endocrinology (1995) 145, 113–119


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


2001 ◽  
pp. 659-665 ◽  
Author(s):  
SN De Biasi ◽  
LI Apfelbaum ◽  
ME Apfelbaum

OBJECTIVE: The purpose of this work was to study the direct effect of leptin on LH release by anterior pituitary glands from female rats at the time of spontaneous and steroid-induced LH surge. METHODS: LH responsiveness to leptin by pituitaries from rats killed in the afternoon (1500 h) at different stages of the 4-day estrous cycle (diestrus-1: D1; diestrus-2: D2; proestrus; estrus), ovariectomized (OVX; 15 days post-castration) and ovariectomized steroid-primed (OVX-E(2)/Pg; pretreated with 5 microg estradiol and 1 mg progesterone), was evaluated in vitro. Hemi-adenohypophyses were incubated in the presence of synthetic murine leptin for 3 h. RESULTS: Addition of increasing concentrations of leptin (0.1-100 nmol/l) to the incubation medium of proestrus pituitaries produced a dose-related stimulation of LH release; the maximal increase to 315% of control was obtained with 10 nmol/l leptin. Leptin (10 nmol/l) enhanced LH release at all days of the estrous cycle, the greatest response occurring in proestrus (318%) and the lowest at D1 (123%). In order to evaluate the role of nitric oxide (NO) in the action of leptin on LH release, glands from proestrus rats were incubated in the presence of 10 nmol/l leptin with or without 0.3 mmol/l N(G)-monomethyl-l-arginine (NMMA), a competitive inhibitor of NO synthase (NOS). NMMA completely suppressed the stimulation of LH release induced by leptin. Leptin also stimulated LH release by pituitaries from OVX rats, and treatment with steroid hormones led to a marked increase in the response (OVX: 162% compared with OVX-E(2)/Pg: 263%; P<0.05). For comparative analysis, a similar experimental procedure was carried out using GnRH (10 nmol/l). Leptin acts at the pituitary level in a similar manner as GnRH, although with significantly lower potency. CONCLUSIONS: These results confirm and extend previous reports regarding a direct action of leptin at the pituitary level, stimulating LH release by anterior pituitaries from female rats at the time of spontaneous and steroid-induced LH surge. In the female rat pituitary this leptin action is controlled by gonadal steroids and mediated by NO.


1991 ◽  
Vol 130 (2) ◽  
pp. 169-175 ◽  
Author(s):  
T. Battmann ◽  
S. Mélik Parsadaniantz ◽  
B. Jeanjean ◽  
B. Kerdelhué

ABSTRACT The effects of substance P (SP) on the preovulatory surge of LH and on the inhibitory and stimulatory effects of oestradiol-17β and progesterone on gonadotrophin-releasing hormone (GnRH)-induced LH release were investigated in vivo and in vitro in the rat. A single s.c. injection of 100 μg SP at 12.00 h on the day of pro-oestrus significantly decreased the preovulatory surge of LH. In vitro, the inhibitory effect of oestradiol-17β on GnRH-induced LH release was not modified by treatment with SP. The stimulatory effect of progesterone on GnRH-induced LH release was reduced by treatment with SP. It is concluded that SP may play a modulatory role in the neuroendocrine control of the preovulatory LH surge. Journal of Endocrinology (1991) 130, 169–175


1982 ◽  
Vol 95 (1) ◽  
pp. 43-48 ◽  
Author(s):  
R. Bhanot ◽  
M. Wilkinson

We have investigated the effects of repeated flurothyl-induced seizures on reproductive function in the female rat. This treatment rapidly induced a state of pseudopregnancy in intact cyclic rats. Prolactin is clearly implicated in this response since treatment with bromocriptine readily counteracted the influence of the convulsions. The mechanism of action of repeated seizures was further characterized in experiments on ovariectomized rats. Thus, 11 daily convulsions, but not a single acute seizure, were able to inhibit the positive feedback effect of progesterone on LH and FSH release in oestrogen-primed animals. In this model also the pituitary gland response to gonadotrophin releasing hormone in vitro was significantly reduced. However, the convulsions had no effect on basal serum or basal in-vitro secretion of LH and FSH in ovariectomized or oestrogen-treated ovariectomized rats. Thus, repeated seizures modified the hypothalamo-pituitary axis in such a way as to prevent it from responding to stimulation. Our results indicate that normal reproductive function in the female rat is very sensitive to repeated seizures and suggest that similar effects may be evident in women subjected to electroconvulsive shock therapy. The successful use of bromocriptine in reversing the influence of seizures in the rat suggests its use in man also.


1981 ◽  
Vol 96 (4) ◽  
pp. 470-474 ◽  
Author(s):  
Peter Ball ◽  
Günter Emons ◽  
Ulrich Gethmann

Abstract. Osmotic minipumps containing low doses of either 4-hydroxyoestradiol or 2-hydroxyoestradiol2) were sc implanted for 152 h (6⅓ day) into immature male and female rats. At the end of the test period the animals were killed and the uterine weight, the vaginal opening, the gonadotrophin serum levels and the gonadal weight monitored. The following results were obtained: 1) a significant increase in the uterine weight and a consistent vaginal opening were observed after 4-hydroxyoestradiol but not after 2-hydroxyoestradiol treatment, 2) LH-levels increased after 2-hydroxyoestradiol but not after 4-hydroxyoestradiol; the increase was, however, not significant, 3) FSH-levels and gonadal weights were lowered by 4-hydroxyoestradiol treatment in male animals only; 2-hydroxyoestradiol had no effect on FSH-levels in both sexes, 4) in no instance an antioestrogenic effect of either catecholoestrogen was observed. It is concluded that 4-hydroxyoestrogens — using the above paradigm — have a significant importance on uterine growth and vaginal opening but (on day 6) no role on LH-release, whereas 2-hydroxyoestrogens may increase LH levels (on day 6) but are nearly ineffective with respect to peripheral parameters.


Author(s):  
Luciano Cardoso Santos ◽  
Jeane Martinha dos Anjos Cordeiro ◽  
Larissa da Silva Santana ◽  
Bianca Reis Santos ◽  
Erikles Macêdo Barbosa ◽  
...  

Abstract The Kisspeptin/Kiss1r system is a key regulator of reproduction by stimulating gonadotrophin-releasing hormone (GnRH) and luteinizing hormone (LH) release, and in vitro studies have shown that Kisspeptin can modulate angiogenesis and immune function, factors that are also essential for reproduction However, there are no studies on the expression of Kisspeptin/Kiss1r at the maternal-fetal interface in domestic cats and its relationship with angiogenic and immunological mediators. Thus, our objective was to evaluate the spatiotemporal expression profile of Kisspeptin/Kiss1r and angiogenic and immunological mediators in the uterus and placenta of domestic cats during pregnancy. Uterus and placenta samples were collected from cats in mid pregnancy (N = 6) and late pregnancy (N = 6), in addition to uterus from non-pregnant cats in diestrus (N = 7), to evaluate protein and gene expression of Kiss1, Kiss1r, VEGF, Flk-1, PLGF, INFγ, MIF, TNFα, IL6, and IL10 by immunohistochemistry and qPCR. Pregnancy increased the uterine expression of Kiss1 and Kiss1r, especially at the late pregnancy, in addition to upregulating INFy, MIF, Vegf, Il10, and Tnf and downregulating Plgf. Higher placental expression of Kiss1r and Plgf mRNA occurred at the late pregnancy, while the expression of Kiss1, VEGF, Flk-1, INFy, TNFα, Il6, and IL10 was higher in the mid of pregnancy. A positive correlation between Kiss1 and Tnf was observed in the placenta, while Kiss1r had a negative correlation with Infγ, Il6, and Il10. The findings reveal that Kisspeptin/Kiss1r and angiogenic and immunological mediators at the maternal-fetal interface of pregnant cat have a gene correlation and are modulated by the gestational age. These data suggest possible functional links of Kisspeptin in placental angiogenesis and immunology.


1977 ◽  
Vol 72 (1) ◽  
pp. 17-26 ◽  
Author(s):  
A. H. PAYNE ◽  
R. P. KELCH ◽  
E. P. MURONO ◽  
J. T. KERLAN

SUMMARY Hypothalamic content of gonadotrophin-releasing hormone (GnRH), serum LH and FSH, capacity of the testis to synthesize testosterone in vitro, and testicular 5-ene-3β-hydroxysteroid dehydrogenase-isomerase and 17β-hydroxysteroid dehydrogenase were measured in groups of rats at approximately 5 day intervals from birth to day 64 and at days 74 and 89. The capacity of the testes to synthesize testosterone in vitro was measured in the presence of a saturating dose of rat LH. Gonadotrophin-releasing hormone increased steadily from 0·17 ng per hypothalamus at birth to a maximum of 7 ng at day 52 and then remained constant. LH concentrations were highly variable and often exceeded adult values between days 10 and 32. After day 32 a steady rise was observed which reached adult values between days 37 and 42. FSH concentrations markedly increased from 255 ng/ml observed at birth and day 10 to a peak value of 1000 ng/ml at day 32. Subsequently there was a steady decline in FSH values until day 74 when the concentration returned to values found at birth. 5-ene-3β-Hydroxysteroid dehydrogenase-isomerase activity exhibited a rapid increase between days 12 and 19 followed by an even greater rate of increase between days 19 and 32 when adult levels were attained. 17β-Hydroxysteroid dehydrogenase activity was very low between birth and day 22. Enzyme activity began to increase at day 22 with a rapid increase in activity observed between days 37 and 58. The increase in capacity to synthesize testosterone closely followed the increase in 17β-hydroxysteroid dehydrogenase activity. The study demonstrates that during sexual maturation in the male rat, changes in serum LH and FSH do not reflect changes in hypothalamic GnRH. The appearance of Leydig cells as monitored by 5-ene-3β-hydroxysteroid dehydrogenase-isomerase activity precedes by approximately 20 days the increase in testicular capacity to synthesize testosterone in vitro. The latter coincides with the increase in 17β-hydroxysteroid dehydrogenase activity. These results suggest that 17β-hydroxysteroid dehydrogenase is a limiting factor in the ability of the testis to respond to LH stimulation.


2017 ◽  
Vol 233 (3) ◽  
pp. 281-292 ◽  
Author(s):  
Kinuyo Iwata ◽  
Yuyu Kunimura ◽  
Keisuke Matsumoto ◽  
Hitoshi Ozawa

Hyperandrogenic women have various grades of ovulatory dysfunction, which lead to infertility. The purpose of this study was to determine whether chronic exposure to androgen affects the expression of kisspeptin (ovulation and follicle development regulator) or release of luteinizing hormone (LH) in female rats. Weaned females were subcutaneously implanted with 90-day continuous-release pellets of 5α-dihydrotestosterone (DHT) and studied after 10 weeks of age. Number of Kiss1-expressing cells in both the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) was significantly decreased in ovary-intact DHT rats. Further, an estradiol-induced LH surge was not detected in DHT rats, even though significant differences were not observed between DHT and non-DHT rats with regard to number of AVPV Kiss1-expressing cells or gonadotrophin-releasing hormone (GnRH)-immunoreactive (ir) cells in the presence of high estradiol. Kiss1-expressing and neurokinin B-ir cells were significantly decreased in the ARC of ovariectomized (OVX) DHT rats compared with OVX non-DHT rats; pulsatile LH secretion was also suppressed in these animals. Central injection of kisspeptin-10 or intravenous injection of a GnRH agonist did not affect the LH release in DHT rats. Notably, ARC Kiss1-expressing cells expressed androgen receptors (ARs) in female rats, whereas only a few Kiss1-expressing cells expressed ARs in the AVPV. Collectively, our results suggest excessive androgen suppresses LH surge and pulsatile LH secretion by inhibiting kisspeptin expression in the ARC and disruption at the pituitary level, whereas AVPV kisspeptin neurons appear to be directly unaffected by androgen. Hence, hyperandrogenemia may adversely affect ARC kisspeptin neurons, resulting in anovulation and menstrual irregularities.


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