Administration of a GnRH-antagonist to immature rats affects subsequent female and male pubertal development differently

1989 ◽  
Vol 120 (6) ◽  
pp. 778-784 ◽  
Author(s):  
H. M. van den Dungen ◽  
J. A. M. J. van Dieten ◽  
F. J. H. Tilders ◽  
G. P. van Rees ◽  
J. Schoemaker
Keyword(s):  
Gnrh Antagonist ◽  
Pubertal Development ◽  
Female Rats ◽  
Female Rat ◽  
Vaginal Opening ◽  
Gonadotropin Secretion ◽  
Adult Age ◽  
Immature Male ◽  
Male And Female Rats ◽  
Testicular Weight

Abstract. Gonadotropin secretion was inhibited in immature male and female rats by sc administration of the GnRH-antagonist ORG30276 (GnRH-A) on days 6, 9, 12 and 15. In GnRH-A-treated females this resulted in suppression of the temporarily increased plasma LH and FSH levels, which normally occur in prepubertal female rats. Ovarian weight was decreased. Although vaginal opening in GnRH-A-treated rats occurred earlier, the age of 1st estrus and the number of ova shed at first ovulation were not affected. Fertility at 4 months of age was normal. After initial suppression of gonadotropin levels, the FSH levels in GnRH-A-treated males, however, sharply increased to about twice the control levels. Plasma FSH remained elevated at least until 4 months of age. The LH levels at adult age were not affected by antagonist treatment and neither were testosterone levels. Testicular weight was decreased by GnRH-A from about 50% on day 15 to about 30% at 4 months of age. Pubertal development as measured by balano-preputial separation was delayed by about 7–10 days. At 4 months of age fertility was decreased. Thus, suppression of early gonadotropin secretion by GnRH-A treatment had dramatic effects on subsequent pubertal development in the male, but not in the female rat.

Ontogeny of sex differences in LH and FSH levels 48 h after castration in the rat

1981 ◽  
Vol 241 (6) ◽  
pp. E460-E464
Author(s):  
J. R. Lorenzen ◽  
J. A. Ramaley
Keyword(s):  
Follicle Stimulating Hormone ◽  
Female Rats ◽  
Hormonal Changes ◽  
Vaginal Opening ◽  
Immature Female ◽  
Immature Male ◽  
Male And Female Rats ◽  
Serum Lh ◽  
Pituitary Secretion ◽  
Serum Gonadotropin

Serum gonadotropin levels were measured 12, 24, and 48 h after gonadectomy in male and female rats (ages, 22--60 days) to assess when during development the rate of rise of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) after castration approximates that seen in the gonadectomized adult. In females serum LH levels 48 h after ovariectomy were increased above sham levels only when the ovaries were removed prior to vaginal opening. Ovariectomy on the day of vaginal opening or at older ages resulted in no increase in LH levels by 48 h after surgery. Serum FSH levels at 24 and 48 h after ovariectomy declined with increasing age at the time of ovariectomy. In males serum LH levels at 48 h after castration increased with increasing age at the time of gonadectomy. Serum FSH levels at either 12, 24, or 48 h after orchidectomy did not change appreciably with age at the time of surgery. It is concluded that the acute pituitary secretion of gonadotropins after removal of testes in the immature male resembles that seen in the mature male early in the course of the development of sexual maturity. In contrast, the acute pituitary secretion of gonadotropins after removal of the ovaries in the immature female does not resemble that seen in the ovariectomized adult until she is mature and capable of ovulating. Thus, the observed delay in the rise of LH seen in ovariectomized adults may be a function of some aspect of the hormonal changes associated with the estrous cycle.

SEX-DEPENDENT PREPUBERTAL GONADOTROPHIN SURGES IN THE RAT

1975 ◽  
Vol 65 (1) ◽  
pp. 91-98 ◽  
Author(s):  
PETER ENEROTH ◽  
JAN-ÅKE GUSTAFSSON ◽  
PAUL SKETT ◽  
ÅKE STENBERG
Keyword(s):  
Sexual Differences ◽  
Female Rats ◽  
Female Rat ◽  
Detection Level ◽  
Male And Female ◽  
Immature Male ◽  
Male And Female Rats ◽  
Second Peak ◽  
Peak Value

SUMMARY The concentrations of LH and FSH were measured by radioimmunoassay in sera from immature male and female rats of various ages. Fairly high levels of FSH were found in both sexes at birth but LH was not detected. FSH peaks appeared in the male at 13 and 19 days of age and in the female at 13 and 17–19 days of age. LH was undetectable in the male before 12 days of age, rose to a peak (440 ± 60 (s.d.) ng/ml) at 13 days of age and fell below the detection level again between 15 and 25 days of age. A further increase then occurred which almost reached adult levels. LH was first detectable in the female rat at 11 days of age with a peak value of 130 ± 35 ng/ml at 12 days. The hormone was undetectable on days 14 and 15, rose to a second peak on day 18 (148 ± 56 ng/ml), and was again absent between 19 and 25 days of age. The concentration rose, as in the male, between days 25 and 28 to a level similar to that of the adult. The results show sexual differences in prepubertal gonadotrophin surges. The LH peak at 12–13 days in both sexes appears to be light-dependent. The FSH peak at this time was affected by light but was not strictly light-dependent.

scholarly journals In Vivo Gonadotropin-Releasing Hormone Secretion in Female Rats during Peripubertal Development and on Proestrus*

Endocrinology ◽  
2001 ◽  
Vol 142 (7) ◽  
pp. 2929-2936 ◽  
Author(s):  
Cheryl L. Sisk ◽  
Heather N. Richardson ◽  
Patrick E. Chappell ◽  
Jon E. Levine
Keyword(s):  
Pubertal Development ◽  
Hormone Secretion ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Female Rats ◽  
Female Rat ◽  
Vaginal Opening ◽  
Pubertal Maturation ◽  
Gnrh Release ◽  
Old Rats

Abstract Pubertal development in female rats is characterized by increased LH levels and the appearance of estrogen-dependent afternoon LH mini-surges. In these studies we performed the first analysis of GnRH patterns in peripubertal rats to determine whether there are similar changes in pulsatile GnRH release. Microdialysis samples were collected at 5-min intervals throughout a 5-h afternoon period from 22 rats sampled on a single day between 30–47 days of age. Adult female rats were sampled on proestrus for comparison. In 30- to 33-day-old rats, GnRH release was infrequent (2.7 pulses/5 h; n = 3), whereas intermediate pulse frequencies were observed in 34- to 37-day-old rats (6.4 pulses/5 h; n = 9) and 38- to 42-day-old (5.0 pulses/5 h; n = 5) rats. The highest GnRH pulse frequencies were observed in 43- to 47-day-old rats (9.4 pulses/5 h; n = 5). Mean GnRH pulse amplitude did not vary significantly with age. Animals sampled before vaginal opening (VO) exhibited significantly slower GnRH pulse frequencies than those sampled after vaginal opening (1.3 pulses/5 h pre-VO vs. 7.6 pulses/5 h post-VO; P= 0.01). An afternoon increase in GnRH secretion, defined operationally as a greater than 25% increase in mean GnRH levels in the last half of the sampling period and tentatively termed a mini-surge, was observed in 0%, 33%, 40%, and 60% of 30- to 33-, 34- to 37-, 38- to 42-, and 43- to 47-day-old rats, respectively. An overall increase in GnRH pulse frequency was observed in females displaying a mini-surge (9.0 pulses/5 h with mini-surge compared with 4.7 pulses/5 h with no mini-surge). The mini-surge itself, however, was associated with a late afternoon increase in GnRH pulse amplitude and not in pulse frequency. In adult proestrous rats, peak levels during the GnRH surge were an order of magnitude greater than those reached in pubertal animals. Our findings demonstrate that pubertal maturation in the female rat is associated with an acceleration of GnRH pulse generator activity and that later stages of pubertal maturation are characterized by the appearance of afternoon increases in GnRH release that may underlie previously reported mini-surges in LH.

GONADOTROPHIN PATTERNS IN MALE AND FEMALE RATS:

1968 ◽  
Vol 58 (4) ◽  
pp. 600-612 ◽  
Author(s):  
Robert Boyd ◽  
Donald C. Johnson
Keyword(s):  
Ascorbic Acid ◽  
Testosterone Propionate ◽  
Female Rats ◽  
Female Rat ◽  
Feedback Effects ◽  
Male And Female ◽  
Prostate Weight ◽  
Male And Female Rats ◽  
Males And Females ◽  
Normal Males

ABSTRACT The effects of various doses of testosterone propionate (TP) upon the release of luteinizing hormone (LH or ICSH) from the hypophysis of a gonadectomized male or female rat were compared. Prostate weight in hypophysectomized male parabiotic partners was used to evaluate the quantity of circulating LH. Hypophyseal LH was measured by the ovarian ascorbic acid depletion method. Males castrated when 45 days old secreted significantly more LH and had three times the amount of pituitary LH as ovariectomized females. Administration of 25 μg TP daily reduced the amount of LH in the plasma, and increased the amount in the pituitary gland, in both sexes. Treatment with 50 μg caused a further reduction in plasma LH in males, but not in females, while pituitary levels in both were equal to that of their respective controls. LH fell to the same low level in partners of males or females receiving 100 μg TP. When gonadectomized at 39 days, males and females had the same amount of plasma LH, but males had more stored hormone. Pituitary levels were unchanged from controls following treatment with 12.5, 25 or 50 μg TP daily, but plasma values dropped an equal amount in both sexes with the latter two doses. Androgenized males or females, gonadectomized when 39 days old, were very sensitive to the effects of TP and plasma LH was significantly reduced with 12.5 μg daily. Pituitary LH in androgenized males was higher than that of normal males but was reduced to normal by small amounts of TP. The amount of stored LH in androgenized females was not different from that of normal females and it was unchanged by any dose of TP tested. Results are consistent with the conclusion that the male hypothalamic-hypophyseal axis is at least as sensitive as the female axis to the negative feedback effects of TP. Androgenization increases the sensitivity to TP in both males and females.

Effect of low doses of continuously administered catecholoestrogens on peripheral and central target organs

1981 ◽  
Vol 96 (4) ◽  
pp. 470-474 ◽  
Author(s):  
Peter Ball ◽  
Günter Emons ◽  
Ulrich Gethmann
Keyword(s):  
Serum Levels ◽  
Female Rats ◽  
Low Doses ◽  
Vaginal Opening ◽  
Uterine Weight ◽  
Central Target ◽  
Male And Female Rats ◽  
Target Organs ◽  
Uterine Growth ◽  
Lh Release

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.

Gonadal steroids effect similar regulation of gonadotrophin subunit mRNA expression in both male and female rats

1992 ◽  
Vol 132 (1) ◽  
pp. 39-45 ◽  
Author(s):  
A. C. Dalkin ◽  
S. J. Paul ◽  
D. J. Haisenleder ◽  
G. A. Ortolano ◽  
M. Yasin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Steady State ◽  
Gnrh Antagonist ◽  
Gonadal Steroids ◽  
Female Rats ◽  
Plasma Testosterone ◽  
Subunit Gene ◽  
Gnrh Secretion ◽  
Male And Female Rats ◽  
Males And Females

ABSTRACT Gonadal steroids can act both indirectly via gonadotrophin-releasing hormone (GnRH) and directly on the pituitary to regulate gonadotrophin subunit gene expression. Recent studies to assess a possible direct action at the pituitary have shown that testosterone, when given to males in the absence of endogenous GnRH action, selectively increases FSH-β mRNA concentrations. Conversely, in females, oestradiol appears to regulate gonadotrophin subunit mRNAs primarily via GnRH. The present study was designed to determine whether these differing results reflect specific actions of the gonadal steroids themselves or different responses of the pituitary gonadotroph cells in males and females. Rats which had been castrated 7 days earlier were given silicone elastomer implants (s.c.) containing oestradiol (plasma oestradiol 68 ± 4 ng/l) in males or testosterone (plasma testosterone 3·5 ± 0·3 μg/l) in females in the absence or presence of a GnRH antagonist. Seven days later pituitaries were removed and steady-state mRNA concentrations measured by dotblot hybridization. In males, oestradiol reduced LH-β and FSH-β but not α mRNA. The antagonist reduced levels of all three subunit mRNAs in males and the addition of oestradiol had no further effect, suggesting that oestradiol regulates gonadotrophin subunit gene expression in males by suppressing GnRH secretion. In females, testosterone reduced all three subunit mRNAs though FSH-β remained threefold higher than in intact animals. The GnRH antagonist was as effective as testosterone alone and reduced α and LH-β to levels found in intact animals. FSH-β mRNA was partially reduced by antagonist alone in ovariectomized females but the addition of testosterone increased FSH-β twofold versus antagonist alone (as has been observed in males). These findings, together with earlier data, suggest that testosterone increased FSH-β twofold versus antagonist alone (as has been observed in males). These findings, together with earlier data, suggest that testosterone reduces gonadotrophin subunit mRNAs by inhibiting GnRH secretion and also acts directly on the gonadotroph to increase steady-state FSH-β mRNA concentrations in both males and females. Journal of Endocrinology (1992) 132, 39–45

scholarly journals Glutathione Conjugates of Ochratoxin a as Biomarkers of Exposure / Glutationski Konjugati Okratoksina A Kao Biomarkeri Izloženosti

2012 ◽  
Vol 63 (4) ◽  
pp. 417-427 ◽  
Author(s):  
Mariana Tozlovanu ◽  
Delphine Canadas ◽  
Annie Pfohl-Leszkowicz ◽  
Christine Frenette ◽  
Robert J. Paugh ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Rat Kidney ◽  
Female Rats ◽  
Amide Bond ◽  
Male Rats ◽  
Dark Agouti ◽  
Female Rat ◽  
Male And Female ◽  
Male And Female Rats ◽  
Liver And Kidney

AbstractIn the present study the photoreactivity of the fungal carcinogen ochratoxin A (OTA) has been utilised to generate authentic samples of reduced glutathione (GSH) and N-acetylcysteine (NAC) conjugates of the parent toxin. These conjugates, along with the nontoxic OTα, which is generated through hydrolysis of the amide bond of OTA by carboxypeptidase A, were utilised as biomarkers to study the metabolism of OTA in the liver and kidney of male and female Dark Agouti rats. Male rats are more susceptible than female rats to OTA carcinogenesis with the kidney being the target organ. Our studies show that the distribution of OTA in male and female rat kidney is not significantly different. However, the extent of OTA metabolism was greater in male than female rats. Much higher levels of OTα were detected in the liver compared to the kidney, and formation of OTα is a detoxification pathway for OTA. These findings suggest that differences in metabolism between male and female rats could provide an explanation for the higher sensitivity of male rats to OTA toxicity

scholarly journals Intrasplenic Transplantation of Isolated Adult Rat Hepatocytes

2011 ◽  
Vol 40 (1) ◽  
pp. 83-92 ◽  
Author(s):  
Meena R. Sharma ◽  
Wojciech Dworakowski ◽  
Bernard H. Shapiro
Keyword(s):  
Cytochrome P450 ◽  
Adult Male ◽  
Total Concentration ◽  
Rat Hepatocytes ◽  
Female Rats ◽  
Female Rat ◽  
Male And Female ◽  
Sexual Dimorphisms ◽  
Male And Female Rats ◽  
Male Specific

Adult male and female rat hepatocytes were individually transplanted into the spleens of adult male and female rats. The recipients were euthanized at either eight, sixteen, thirty, or forty-five weeks following transplantation, at which time hepatic and splenic levels of liver-specific rat albumin mRNA as well as sex-dependent transcript levels of CYP2C11, -2C12, -2C7, -2A1, and -3A2—which accounts for > 60% of the total concentration of hepatic constituent cytochrome P450—were determined. Whereas the pre-infused hepatocytes expressed their expected cytochrome P450 sexual dimorphisms (female-specific CYP2C12, male-specific CYP3A2, and female-predominant CYP2A1), their post-transplantational competence now reflected the sexual dimorphisms of the recipient (as observed in the host’s liver), which supports the concept that the sex-dependent growth hormone circulating profiles are the determinants regulating the expression levels of hepatic cytochrome P450. Also expressed at normal concentrations in the pre-infused hepatocytes, male-specific CYP2C11 and female-predominant CYP2C7 were inexplicably undetectable in the spleens of both recipient males and females, regardless of the sex of the donor hepatocytes, almost one year after transplantation.

Desensitization of gonadotropin responses to kisspeptin in the female rat: analyses of LH and FSH secretion at different developmental and metabolic states

2008 ◽  
Vol 294 (6) ◽  
pp. E1088-E1096 ◽  
Author(s):  
J. Roa ◽  
E. Vigo ◽  
D. García-Galiano ◽  
J. M. Castellano ◽  
V. M. Navarro ◽  
...  
Keyword(s):  
Current Data ◽  
Female Rats ◽  
Pharmacological Intervention ◽  
Female Rat ◽  
Continuous Administration ◽  
Gonadotropin Secretion ◽  
Dynamic Regulation ◽  
Intracerebral Administration ◽  
Metabolic States ◽  
Transient Elevation

Kisspeptins have emerged as potent elicitors of gonadotropin secretion and, therefore, putative targets for pharmacological intervention. In this context, desensitization of gonadotropin responses to continuous administration of kisspeptins has begun to be characterized, but information so far available is mostly restricted to LH responses in males, whereas the similar phenomenon in females, of obvious therapeutic interest, remains virtually unexplored. We report herein LH and FSH responses to continuous intracerebral administration of kisspeptin in female rats at different developmental and metabolic states. Infusion of kisspeptin-10 to adult female rats induced a transient elevation in serum LH concentrations, followed by a precipitous drop and normalization of LH levels thereafter. Elevation of LH after kisspeptin infusion was prolonged in underfed animals; a phenomenon mimicked by leptin administration. Conversely, FSH levels were persistently heightened along continuous kisspeptin infusion, but duration of this response was shortened by undernutrition. In pubertal females, LH and FSH levels remained elevated at the end of a 7-day infusion of kisspeptin; responses whose magnitude was augmented by subnutrition but not mimicked by leptin. In all settings, terminal gonadotropin-releasing hormone responses were fully preserved, suggesting that eventual desensitization must occur upstream from the pituitary. In summary, our current data document the pharmacological consequences of continuous administration of kisspeptin to female rats, with remarkable differences being detected between LH and FSH responses, in different developmental and metabolic states. These observations of potential pharmacological interest might help also to delineate the physiological roles of kisspeptins in the dynamic regulation of gonadotropin secretion in the female.

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