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

Micevych, Paul E.; Sinchak, Kevin; Mills, Richard H.; Tao, Leslie; LaPolt, Philip S.; Lu, John

doi:10.1159/000071703

Cited by 129 publications

(152 citation statements)

References 55 publications

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“…Adrenal secretion occurs in concentrations that are typically comparable to ovarian release (Fajer et al 1971, Shaikh & Shaikh 1975. There is also evidence that local P 4 synthesis is present in hypothalamic astrocytes and has been shown to occur in response to estrogen feedback (Micevych et al 2003), linking this effect to generation of the LH surge. However, under the present paradigm, the large and prompt ATRZ-induced elevation in circulating P 4 implicates adrenal P 4 as a principal driving factor in the LH results observed.…”

Section: Discussionmentioning

confidence: 99%

Atrazine-induced elevation or attenuation of the LH surge in the ovariectomized, estrogen-primed female rat: role of adrenal progesterone

et al. 2013

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Multiple exposures to the herbicide atrazine (ATRZ) were shown to suppress the LH surge in both cycling female rats and those ovariectomized (OVX) and primed with estradiol (E 2 ). A single ATRZ administration was found to induce a prompt and marked increase in progesterone (P 4 ). As exogenous P 4 is known to have a differential effect on the LH surge depending on its temporal relationship with the surge, it was hypothesized that a single treatment in an OVX, E 2 -primed rat would augment the surge, whereas several exposures would cause a decrease. Following four daily treatments with 100 mg/kg, LH surge was suppressed. In contrast, a single ATRZ exposure elevated the surge. Two treatments were without effect. The single administration caused a large increase in P 4 at 30 and 60 min that was likely attributable to adrenal secretion. Four exposures also elevated P 4 after the final treatment, although the duration of the increase was shortened. A single treatment with 0, 10, 30, and 100 mg/kg ATRZ showed similar elevations at the highest concentration in P 4 , the LH peak, and area under the curve (AUC), whereas four exposures reduced the AUC. An increase at 1 h in the expression of Kiss1 in the anteroventral periventricular nucleus suggests that this regional kisspeptin neuronal population has a role in the ATRZ augmentation of the surge. These data support the hypothesis that ATRZ-induced changes in adrenal P 4 can either augment or attenuate the surge depending on the temporal proximity of exposure to the rise in LH.

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Section: Discussionmentioning

confidence: 99%

Atrazine-induced elevation or attenuation of the LH surge in the ovariectomized, estrogen-primed female rat: role of adrenal progesterone

et al. 2013

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“…Second, estradiol induced progesterone receptors (PR) in the hypothalamus are needed (Chappell et al, 2000;DePaolo, 1988;Hibbert et al, 1996;Mahesh and Brann, 1992;SanchezCriado et al, 1994;Snyder et al, 1984). Third, preovulatory progesterone is also essential for the gonadotropin surge (DePaolo, 1988;Hibbert et al, 1996;Mahesh et al, 1992;Micevych et al, 2003;Remohi et al, 1988). Most models of the LH surge use both estradiol and progesterone priming because ovariectomized rats treated with only estradiol show a physiological, but blunted LH surge, but treatment with progesterone increases the magnitude and duration of the surge (DePaolo and Barraclough, 1979).…”

Section: Model Of Estrogen Positive Feedbackmentioning

confidence: 99%

“…Thus, levels of a particular steroid in the brain are a composite of steroids from the periphery, converted peripheral steroids, and neurosteroids. Additionally, hormonal steroids also regulate the site-specific synthesis of neurosteroid levels (Maguire and Mody, 2007;Micevych et al, 2003) and their cognate receptors (Chappell and Levine, 2000;MacLusky and McEwen, 1978;Soma et al, 2005) that affect neurosteroid levels and function. Such peripheral sex steroid-neurosteroid interactions are the subject of this review, especially as it relates to neuroprogesterone synthesis.…”

Section: Introductionmentioning

confidence: 99%

Estradiol regulation of progesterone synthesis in the brain

Micevych

Sinchak

2008

Molecular and Cellular Endocrinology

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Steroidogenesis is now recognized as a global phenomenon in the brain, but how it is regulated and its relationship to circulating steroids of peripheral origin have remained more elusive issues. Neurosteroids, steroids synthesized de novo in nervous tissue, have a large range of actions in the brain, but it is only recently that the role of neuroprogesterone in the regulation of arguably the quintessential steroid dependent neural activity, regulation of the reproduction has been appreciated. Circuits involved in controlling the LH surge and sexual behaviors were thought to be influenced by estradiol and progesterone synthesized in the ovary and perhaps the adrenal. It is now apparent that estradiol of ovarian origin regulates the synthesis of neuroprogesterone, and it is the locally produced neuroprogesterone that is involved in the initiation of the LH surge and subsequent ovulation. In this model, estradiol induces the transcription of progesterone receptors while stimulating synthesis of neuroprogesterone. Although the complete signaling cascade has not been elucidated, many of the features have been characterized. The synthesis of neuroprogesterone occurs primarily in astrocytes and requires the interaction of membrane associated estrogen receptor-α with metabotropic glutamate receptor-1a. This G protein-coupled receptor activates a phospholipase C that in turn increases inositol trisphosphate (IP 3 ) levels mediating the release of intracellular stores of Ca 2+ via an IP 3 receptor gated Ca +2 channel. The large increase in free cytoplasmic Ca 2+ ([Ca 2+ ] i ) stimulates the synthesis of progesterone, which can then diffuse out of the astrocyte and activate estradiol-induced progesterone receptors in local neurons to trigger the neural cascade to produce the LH surge. Thus, it is a cooperative action of astrocytes and neurons that is needed for estrogen positive feedback and stimulation of the LH surge.

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“…In the brain, E 2 can enhance the expression of the enzymes that convert P 4 to 3a,5a-THP and can enhance 3a,5a-THP production (Cheng & Karavolas 1973, Micevych et al 2003, Frye & Rhodes 2005. As such, circulating levels of E 2 were assessed and were higher among multiparous compared with primiparous dams.…”

mentioning

confidence: 99%

Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks

Paris¹,

Frye²

2008

Reproduction

116

105

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Ovarian hormone elevations are associated with enhanced learning/memory. During behavioral estrus or pregnancy, progestins, such as progesterone (P 4 ) and its metabolite 5a-pregnan-3a-ol-20-one (3a,5a-THP), are elevated due, in part, to corpora luteal and placental secretion. During 'pseudopregnancy', the induction of corpora luteal functioning results in a hormonal milieu analogous to pregnancy, which ceases after about 12 days, due to the lack of placental formation. Multiparity is also associated with enhanced learning/memory, perhaps due to prior steroid exposure during pregnancy. Given evidence that progestins and/or parity may influence cognition, we investigated how natural alterations in the progestin milieu influence cognitive performance. In Experiment 1, virgin rats (nulliparous) or rats with two prior pregnancies (multiparous) were assessed on the object placement and recognition tasks, when in high-estrogen/P 4 (behavioral estrus) or low-estrogen/P 4 (diestrus) phases of the estrous cycle. In Experiment 2, primiparous or multiparous rats were tested in the object placement and recognition tasks when not pregnant, pseudopregnant, or pregnant (between gestational days (GDs) 6 and 12). In Experiment 3, pregnant primiparous or multiparous rats were assessed daily in the object placement or recognition tasks. Females in natural states associated with higher endogenous progestins (behavioral estrus, pregnancy, multiparity) outperformed rats in low progestin states (diestrus, non-pregnancy, nulliparity) on the object placement and recognition tasks. In earlier pregnancy, multiparous, compared with primiparous, rats had a lower corticosterone, but higher estrogen levels, concomitant with better object placement performance. From GD 13 until post partum, primiparous rats had higher 3a,5a-THP levels and improved object placement performance compared with multiparous rats.

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

Cited by 129 publications

References 55 publications

Atrazine-induced elevation or attenuation of the LH surge in the ovariectomized, estrogen-primed female rat: role of adrenal progesterone

Atrazine-induced elevation or attenuation of the LH surge in the ovariectomized, estrogen-primed female rat: role of adrenal progesterone

Estradiol regulation of progesterone synthesis in the brain

Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks

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