Differential Patterns of Gonadotropin Responses to Ovarian Steroids and to LH-Releasing Hormone Between Constant-Estrous and Pseudopregnant States in Aging Rats1

Lu, John; Damassa, David A.; Gilman, Dennis P.; Judd, Howard L.; Sawyer, Charles H.

doi:10.1095/biolreprod23.2.345

Cited by 70 publications

(42 citation statements)

References 21 publications

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“…Brain and plasma estradiol and progesterone were measured by RIAs [40]. Prior to RIA, plasma (0.25 ml) and homogenized brain samples (∼40 mg) were extracted with diethyl ether, and progesterone and estradiol fractionated by Celite TM column chromatography.…”

Section: Methodsmentioning

confidence: 99%

The Luteinizing Hormone Surge Is Preceded by an Estrogen-Induced Increase of Hypothalamic Progesterone in Ovariectomized and Adrenalectomized Rats

et al. 2003

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As circulating estrogen levels rise on the afternoon of proestrus, they stimulate the hypothalamo-pituitary axis. This estrogen positive feedback is pivotal to stimulate the luteinizing hormone (LH) surge required for ovulation and luteinization of ovarian follicles. In addition to estrogen, pre-LH surge progesterone is critical for an LH surge as was demonstrated by blocking progesterone synthesis. In ovariectomized (OVX) rats treated with trilostane, a blocker of the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD) that catalyzes the conversion of pregnenolone to progesterone, estrogen did not induce an LH surge. Further, estrogen induced an LH surge in OVX and adrenalectomized (ADX) rats, indicating that the source of progesterone was neither the ovary nor adrenal gland. This estrogen-only LH surge was inhibited by pretreatment with trilostane, indicating that although the adrenal gland and ovary were not necessary for positive feedback, progesterone synthesis was critical for estrogen-induced positive feedback in an OVX/ADX rat. This suggested that the LH surge is dependent on the pre-LH surge synthesis of progesterone. Estrogen-induced progesterone receptors in the hypothalamus are vital for the LH surge, so a potential location for progesterone synthesis is the hypothalamus. OVX/ADX female rats were treated with 17β-estradiol (50 µg) and progesterone levels were assayed by RIA. Progesterone levels were elevated in hypothalamic tissue following estrogen treatment. No increases in tissue progesterone levels were found in parietal cortex, cerebellum, medulla, pituitary or plasma. Additionally, male rats that do not have an estrogen positive feedback-induced LH surge were examined. Castrated/ADX male rats had no increase in hypothalamic progesterone levels after estrogen treatment. Together, these data strongly suggest that estrogen enhances neuroprogesterone synthesis in the hypothalamus that is involved in the positive feedback regulating the LH surge.

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Section: Methodsmentioning

confidence: 99%

The Luteinizing Hormone Surge Is Preceded by an Estrogen-Induced Increase of Hypothalamic Progesterone in Ovariectomized and Adrenalectomized Rats

et al. 2003

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“…Plasma concentrations of LH and FSH were measured by double antibody radioimmuno assay (RIA) using previously described methods [15). These RIAs employed the reagents provided by the National Hormone and Pi tuitary Program.…”

Section: Methodsmentioning

confidence: 99%

Alterations in Gonadotropin Secretion in Middle-Aged Persistent-Estrous Rats following LHRH Agonist Treatment

1992

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During aging female rats enter an anovulatory condition with chronically elevated circulating levels of estrogen described as persistent estrus (PE). Since this endocrine state is dramatically different from the fluctuating steroid milieu of young regularly cycling females, interpretations of altered neuroendocrine responses in aged rats have been difficult to attribute to aging per se. In the present study, young cyclic and middle-aged PE rats were treated with an LHRH agonist, [DTrp⁶, Pro⁹-NHEt]-LHRH, continuously (2.5 µg/h) for 12 days to suppress gonadotropin and ovarian steroid secretion. On the evening of the first day of LHRH agonist (LHRH-AG) treatment both young cyclic and middle-aged PE rats showed marked (p < 0.01) increases in plasma LH and FSH followed by progressive decreases in gonadotropin secretion which reached significantly (p < 0.05) lower levels than pretreatment values by day 7. LHRH-AG treatment significantly (p < 0.01) reduced circulating 17β-estradiol (E2) levels in both young and PE rats while progesterone concentrations did not change. Following LHRH-AG treatment, ovariectomy (OVX) resulted in increases of plasma LH and FSH that were delayed and attenuated in PE rats as compared to those of young females. When compared to non-treated rats, 12 days of LHRH-AG treatment in both young and PE females had a minimal and transient effect on the post-OVX gonadotropin responses, suggesting that the endocrine status immediately prior to OVX does not profoundly influence the post-OVX responses in young cyclic and middle-aged PE rats. Furthermore, LHRH-AG treatment does not appear to have permanent inhibitory effects on the hypothalamic-pituitary axis. Following LHRH-AG treatment in intact rats, the rebound in FSH secretion was delayed and prolonged in PE females and these rats did not return to estrous cyclicity. The results of these studies indicate that the neuroendocrine responses to the removal and return of ovarian negative feedback are impaired in PE rats, and suggest that these rats have a permanent dysfunction in the hypothalamic-pituitary-ovarian axis.

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“…The content of gonadotro pin-releasing hormone (GnRH) in the hypothalamus was shown to be similar between old and young female rats [4|. Ad ministration of GnRH induces the same or lower magnitude of increase in the secretion of luteinizing hormone (LH) in old than in young female rats [5,6). LH secretion is increased fol lowing ovariectomy in old and young rats, but the magnitude of the rise is less in old than in young ovariectomized (Ovx) rats [7].…”

mentioning

confidence: 99%

Age-Related Differences in the Release of Luteinizing Hormone and Gonadotropin-Releasing Hormone in Ovariectomized Rats

Hwang

Pu²,

Hwang³

et al. 1990

Neuroendocrinology

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The effect of aging on the release of gonadotropin-releasing hormone (GnRH) in vitro and of luteinizing hormone (LH) both in vivo and in vitro in ovariectomized (Ovx) rats was studied. Old (21–24 months) and young (3–4 months) rats were Ovx before use. They were injected subcutaneously with estradiol benzoate (25 µg/kg) or sesame oil for 3 days and then challenged with GnRH (0.5,2 or 10 µg/kg) via a jugular catheter. Blood samples were collected immediately before and at 5, 10, 20, 40 and 60 min following GnRH injection. For in vitro study, Ovx rats were decapitated. The anterior pituitary glands (APs) were incubated with GnRH (0.1 or 10 nM) and estradiol (0, 0.1, 1 or 10 nM) at 37 ^¤C for 30 min. The mediobasal hypothalamus was superfused with Locke’s solution at 37 °C for 210 min, and stimulated with 60 mM KCl at 90 and 150 min. The medium samples were collected at 10-min intervals. Concentrations of GnRH and LH in plasma and medium samples were measured by radioimmunoassay. In all rats, the basal and GnRH-stimulated levels of plasma LH were lower in old than in young rats. The spontaneous release of LH in vitro from APs of Ovx rats was increased by aging, whereas GnRH-stimulated release of LH in vitro was lower in old than in young animals. The potassium-stimulated, but not spontaneous, release of GnRH was lower in old than in young Ovx rats. These results suggest that the reduction of plasma LH level in female rats during aging is in part due to a decrease in the K⁺-stimulated release of GnRH, and a reduction of pituitary responsiveness to GnRH and estradiol.

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Differential Patterns of Gonadotropin Responses to Ovarian Steroids and to LH-Releasing Hormone Between Constant-Estrous and Pseudopregnant States in Aging Rats1

Cited by 70 publications

References 21 publications

The Luteinizing Hormone Surge Is Preceded by an Estrogen-Induced Increase of Hypothalamic Progesterone in Ovariectomized and Adrenalectomized Rats

The Luteinizing Hormone Surge Is Preceded by an Estrogen-Induced Increase of Hypothalamic Progesterone in Ovariectomized and Adrenalectomized Rats

Alterations in Gonadotropin Secretion in Middle-Aged Persistent-Estrous Rats following LHRH Agonist Treatment

Age-Related Differences in the Release of Luteinizing Hormone and Gonadotropin-Releasing Hormone in Ovariectomized Rats

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