Interaction of Gonadal Steroids and Gonadotropin-Releasing Hormone on Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and PACAP Receptor Expression in Cultured Rat Anterior Pituitary Cells

Zheng, Weiming; Grafer, Constance M.; Halvorson, Lisa M.

doi:10.1177/1933719113488454

Cited by 8 publications

(4 citation statements)

References 69 publications

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“…Expression of PACAP receptor mRNA was decreased by GnRH treatment, and minimally increased by DHT treatment, but was not altered by the addition of estradiol or progesterone. DHT and GnRH together blunted PACAP receptor gene expression (166). Grafer and Halvorson (167) confirmed the regulatory role of androgens in the function of PACAP.…”

Section: Interactions Between Pacap Gnrh and Sex Steroidsmentioning

confidence: 88%

Current State of Understanding of the Role of PACAP in the Hypothalamo-Hypophyseal Gonadotropin Functions of Mammals

et al. 2020

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PACAP was discovered 30 years ago in Dr. Akira Arimura's laboratory. In the past three decades since then, it has become evident that this peptide plays numerous crucial roles in mammalian organisms. The most important functions of PACAP are the following: 1. neurotransmitter, 2. neuromodulator, 3. hypophysiotropic hormone, 4. neuroprotector. This paper reviews the accumulated data regarding the distribution of PACAP and its receptors in the mammalian hypothalamus and pituitary gland, the role of PACAP in the gonadotropin hormone secretion of females and males. The review also summarizes the interaction between PACAP, GnRH, and sex steroids as well as hypothalamic peptides including kisspeptin. The possible role of PACAP in reproductive functions through the biological clock is also discussed. Finally, the significance of PACAP in the hypothalamo-hypophysial system is considered and the facts missing, that would help better understand the function of PACAP in this system, are also highlighted.

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Section: Interactions Between Pacap Gnrh and Sex Steroidsmentioning

confidence: 88%

Current State of Understanding of the Role of PACAP in the Hypothalamo-Hypophyseal Gonadotropin Functions of Mammals

et al. 2020

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“…We speculate that the reduction in PACAP mRNA expression that occurred during development in both sexes, the fact that no fasting‐induced changes in PACAP mRNA expression were observed in either sex, and the reduction in PAC1 mRNA expression seen during fasting in male rats might be involved in the physiological mechanisms responsible for maintaining appetite and promoting growth in the pre‐pubertal period. It has been reported that pituitary PACAP and PAC1 mRNA expression are regulated by gonadal steroids (Zheng et al, 2014). Thus, we also speculate that differences in the gonadal steroidal milieu might be responsible for the sexual dimorphism in hypothalamic PAC1 mRNA levels seen under basal and fasted conditions in the present study.…”

Section: Discussionmentioning

confidence: 99%

Developmental changes in the hypothalamic mRNA expression levels of PACAP and its receptor PAC1 and their sensitivity to fasting in male and female rats

Iwasa

Matsuzaki

Tungalagsuvd

et al. 2016

Intl J of Devlp Neuroscience

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The actions and responses of hypothalamic appetite regulatory and factors change markedly during the neonatal to pre-pubertal period. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been found to play pivotal roles in the regulation of metabolic and nutritional status through its specific receptor PAC1. PACAP/PAC1 have anorectic roles, and their functions are regulated by leptin in adulthood. In the present study, we showed that hypothalamic PACAP mRNA expression decreases during the neonatal to pre-pubertal period (from postnatal day 10-30) in both male and female rats. During this period, hypothalamic PACAP mRNA expression was not affected by 24h fasting in either sex, while the serum leptin levels (leptin is a positive regulator of hypothalamic PACAP expression in adulthood) of both sexes were decreased by fasting. On the other hand, hypothalamic PAC1 mRNA expression did not change during the neonatal to pre-pubertal period in either sex; however, its levels were consistently higher in males than in females. Hypothalamic PAC1 mRNA expression was decreased by 24h fasting in males, but no such changes were observed in females. These results indicate while hypothalamic PACAP expression is sensitive to a negative energy state and the serum leptin level in adulthood, no such relationships are seen in the pre-pubertal period. In addition, we speculate that differences in the gonadal steroidal milieu might induce sexual dimorphism in the basal hypothalamic PAC1 mRNA level and its response to fasting. The mechanisms responsible for and the physiological effects of such changes in hypothalamic PACAP and PAC1 expression during the developmental period remain to be clarified.

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“…Our laboratory is also interested in regulation of the autocrine–paracrine factor pituitary adenylate-cyclase polypeptide (PACAP, Adcyap1) and we have reported the ability of P4 to augment GnRH-mediated stimulation on PACAP mRNA levels by approximately 3-fold using a similar paradigm. 75 In terms of the LβT2 cells, the majority of prior studies have used these cells to analyze for transcriptional activation using luciferase expression rather than mRNA levels as an end point, with the exception of a response to GnRH. It was therefore not possible to identify an obvious positive mRNA control for steroid responsiveness.…”

Section: Discussionmentioning

confidence: 99%

Gonadotropin-Releasing Hormone and Gonadal Steroids Regulate Transcription Factor mRNA Expression in Primary Pituitary and Immortalized Gonadotrope Cells

et al. 2015

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Hormonal regulation of pituitary gonadotropin gene expression has been attributed to gonadotropin-releasing hormone (GnRH)-mediated stimulation of immediate early gene expression and gonadal steroid interactions with their respective nuclear receptors. A number of orphan nuclear receptors including steroidogenic factor 1, liver receptor homologue 1, dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1, and chicken ovalbumin upstream promoter-transcription factors I/II as well as the GATA family members, GATA2 and GATA4, have also been implicated in transcriptional regulation of the gonadotropin genes. We hypothesized that hormonally mediated changes in these latter transcription factors may provide an additional mechanism for mediating hormonal effects beyond the more classically appreciated pathways. In these studies, we demonstrate significant regulation of orphan nuclear receptor and GATA messenger RNA levels by GnRH, dihydrotestosterone, estradiol, and progesterone in both cultured primary pituitary cells and gonadotrope-derived cell line, LβT2. These results advance our understanding of the complex mechanisms by which GnRH and steroid hormones achieve precise regulation of anterior pituitary function.

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Interaction of Gonadal Steroids and Gonadotropin-Releasing Hormone on Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and PACAP Receptor Expression in Cultured Rat Anterior Pituitary Cells

Cited by 8 publications

References 69 publications

Current State of Understanding of the Role of PACAP in the Hypothalamo-Hypophyseal Gonadotropin Functions of Mammals

Current State of Understanding of the Role of PACAP in the Hypothalamo-Hypophyseal Gonadotropin Functions of Mammals

Developmental changes in the hypothalamic mRNA expression levels of PACAP and its receptor PAC1 and their sensitivity to fasting in male and female rats

Gonadotropin-Releasing Hormone and Gonadal Steroids Regulate Transcription Factor mRNA Expression in Primary Pituitary and Immortalized Gonadotrope Cells

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