Alterations in Luteinizing Hormone-Releasing Hormone Release from the Mediobasal Hypothalamus of Ovariectomized, Steroid-Primed Middle-Aged Rats as Measured by Push-Pull Perfusion

Rubin, Beverly S.; Bridges, Robert S.

doi:10.1159/000125121

Cited by 83 publications

(45 citation statements)

References 18 publications

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“…The decreased LHRH release was also supported by the slow and low increase in plasma LH after progesterone treatment in old females. Rubin et al(1989) recently observed with the push-pull perfusion technique that the mean levels of LHRH in perfusates in estrogen and progesteronetreated middle-aged females (10-12 months) were lower than those in young females. If, similarly to their rats, less LHRH was released from the ME to the portal circulation in our old rats, a difference between the plasma LH concentrations in the two age groups would result.…”

Section: Discussionmentioning

confidence: 98%

Hypothalamic Luteinizing Hormone-Releasing Hormone(LHRH) and LH Secretion in Aging Female Rats.

1990

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Age-related changes in hypothalamic luteinizing hormone-releasing hormone (LHRH) and luteinizing hormone (LH) secretion were studied in young (6 months), middle-aged (12 months) and old (18 months) female rats. The LHRH levels in the mid-hypothalamic area were higher in intact middle-aged and old females than in young ones.Additionally, there was no age difference in the hypothalamic LHRH levels in male rats. In order to clarify the significance of this age-related increase in female rats, we examined the effects of progesterone treatment in estrogen-primed ovariectomized young and old rats on the LHRH levels in the median eminence (ME) and on plasma LH levels. We found phasic changes in ME-LHRH and plasma LH levels in estrogenprimed rats following progesterone treatment in rats of both ages, but the progesterone-induced change in ME-LHRH levels tended to be delayed in old rats compared with young females.This delay may correspond to the delayed onset, slow and low magnitude of plasma LH increase in old females. The ME-LHRH levels were generally higher in old rats than in young rats. Nevertheless, we found that the increase in plasma LH in response to progesterone treatment in estrogen-primed ovariectomized females was smaller in old rats than young rats.These results suggest that the LHRH secretory mechanism changes with age in female rats.Such alterations may result in the accumulation of LHRH in the mid-hypothalamic area and an increase in ME-LHRH.

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Section: Discussionmentioning

confidence: 98%

Hypothalamic Luteinizing Hormone-Releasing Hormone(LHRH) and LH Secretion in Aging Female Rats.

1990

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“…Using age-appropriate rats at young, middle-aged, and old ages, we ovariectomize the animals, wait 1 month, and then give ET (i.e., estradiol), with or without progestins, in physiologically relevant dosages Yin and Gore, 2006). Another important difference between primates and rodents is that postmenopausal increases in GnRH or surrogates for GnRH (e.g., gonadotropins or gonadotropin-free a subunit) occur during the perimenopause (Hall and Gill, 2001;Maffucci and Gore, 2006), whereas in rodents, GnRH neurosecretion and the preovulatory GnRH/LH surge declines at estropause (Rubin and Bridges, 1989).…”

Section: Patterns Of Reproductive Senescence Differ Across Speciesmentioning

confidence: 99%

“…(2) Acyclic old rats can be induced to ovulate by neurochemical, hormonal, or social stimuli (for review, see Gore, 2001). (3) Pulsatile GnRH release decreases in middle-aged rats (Rubin and Bridges, 1989) and increases in perimenopausal rhesus monkeys . Although there are species differences in these phenomena, both of these changes precede actual reproductive failure.…”

Section: The Circuitry Driving Gnrh Neurons Undergoes Age-related Chamentioning

confidence: 99%

Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women

Morrison¹,

Brinton²,

Schmidt³

et al. 2006

J. Neurosci.

312

242

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IntroductionAs neuroscientists, we can be so taken by the complexity and unique capabilities of the brain that we occasionally forget that it is part of a larger integrated biological system reliant on signaling and communication throughout the organism. The interactions between key organs that release hormones (e.g., gonads) and the nervous system are an excellent reflection of this "whole-brain, whole-body" level of integration. For example, effects of estrogens such as 17-␤-estradiol (the major estrogen in most mammals, including women, referred to henceforward as estradiol) on a broad array of brain regions and the widespread distribution of estrogen receptors throughout the entire brain highlight the extraordinary integrative power of this hormone. An important concept in this interaction is that the brain both controls estrogen release through the hypothalamus-pituitary-gonadal (HPG) axis and responds to estrogen. Neuroendocrine function initiates in the hypothalamus (see below, section by A.C.G.) (Fig. 1), but the circuits that respond to estrogens go well beyond the hypothalamus to include neocortex, hippocampus, and brainstem. In addition, estradiol plays a key role in the neurobiology of aging, because endocrine and neural senescence overlap in time and are mechanistically intertwined in complex feedback loops. This aspect of aging is fundamental for humans, because all women will experience a dramatic drop in circulating estrogens if they live long enough to reach the menopause transition. Interestingly, at the turn of the past century, both life expectancy and the average age of onset of menopause for women in America was slightly over 50 years, whereas currently women can expect to live until 80 years of age, although the average age of menopause remains in

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“…It should be noted that additional changes in GnRH activity have been reported by investigators who have utilized rats that have reached more advanced stages of reproductive senescence, particularly during times of increased demand on the population of GnRH neurons. These changes include decreased in vivo output of GnRH in conjunction with the steroidinduced LH surge using push-pull perfusion (Rubin and Bridges, 1989) and decreased LH pulse frequency and amplitude in ovariectomized rats (Scarbrough FIG. 1.…”

Section: Changes In the Pattern Of Gonadotropin Secretion Reflecmentioning

confidence: 99%

Neuroendocrine Modulation and Repercussions of Female Reproductive Aging

Wise

Smith

Dubal

et al. 2002

Recent Progress in Hormone Research

104

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The menopause marks the end of a woman's reproductive life. During the postmenopausal period, plasma estrogen concentrations decrease dramatically and remain low for the rest of her life, unless she chooses to take hormone replacement therapy. During the past 20 years, we have learned that changes in the central nervous system are associated with and may influence the timing of the menopause in women. Recently, it has become clear that estrogens act on more than just the hypothalamus, pituitary, ovary, and other reproductive organs. In fact, they play roles in a wide variety of nonreproductive functions. With the increasing life span of humans from approximately 50 to 80 years and the relatively fixed age of the menopause, a larger number of women will spend over one third of their lives in the postmenopausal state. It is not surprising that interest has increased in factors that govern the timing of the menopause and the repercussions of the lack of estrogen on multiple aspects of women's health. We have used animal models to better understand the complex interactions between the ovary and the brain that lead to the menopause and the repercussions of the hypoestrogenic state. Our results show that when rats reach middle age, the patterns and synchrony of multiple neurochemical events that are critical to the preovulatory gonadotropin-releasing hormone (GnRH) surge undergo subtle changes. The precision of rhythmic pattern of neurotransmitter dynamics depends on the presence of estradiol. Responsiveness to this hormone decreases in middle-aged rats. The lack of precision in the coordination in the output of neural signals leads to a delay and attenuation of the luteinizing hormone surge, which lead to irregular estrous cyclicity and, ultimately, to the cessation of reproductive cycles. We also have examined the impact of the lack of estrogen on the vulnerability of the brain to injury. Our work establishes that the absence of estradiol increases the extent of cell death after stroke-like injury and that treatment with low physiological levels of estradiol are profoundly neuroprotective. We have begun to explore the cellular and molecular mechanisms that underlie this novel nonreproductive action of estrogens. In summary, our studies show that age-related changes in the ability of estradiol to coordinate the neuroendocrine events that lead to regular preovulatory GnRH surges contribute to the onset of irregular estrous cycles and eventually to acyclicity. Furthermore, we have shown that the lack of estradiol increases the vulnerability of the brain to injury and neurodegeneration.

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Alterations in Luteinizing Hormone-Releasing Hormone Release from the Mediobasal Hypothalamus of Ovariectomized, Steroid-Primed Middle-Aged Rats as Measured by Push-Pull Perfusion

Cited by 83 publications

References 18 publications

Hypothalamic Luteinizing Hormone-Releasing Hormone(LHRH) and LH Secretion in Aging Female Rats.

Hypothalamic Luteinizing Hormone-Releasing Hormone(LHRH) and LH Secretion in Aging Female Rats.

Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women

Neuroendocrine Modulation and Repercussions of Female Reproductive Aging

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