scholarly journals Mechanisms of Central Hypogonadism

2021 ◽  
Vol 22 (15) ◽  
pp. 8217
Author(s):  
Thomas M. Barber ◽  
Ioannis Kyrou ◽  
Gregory Kaltsas ◽  
Ashley B. Grossman ◽  
Harpal S. Randeva ◽  
...  
Keyword(s):  
Reproductive Function ◽  
Leptin Resistance ◽  
Neural Signals ◽  
Dual Purpose ◽  
Hpg Axis ◽  
Physical Trauma ◽  
Common Causes ◽  
Fat Stores ◽  
Androgenic Steroids ◽  
External Signals

Reproductive function depends upon an operational hypothalamo–pituitary–gonadal (HPG) axis. Due to its role in determining survival versus reproductive strategies, the HPG axis is vulnerable to a diverse plethora of signals that ultimately manifest with Central Hypogonadism (CH) in all its many guises. Acquired CH can result from any pituitary or hypothalamic lesion, including its treatment (such as surgical resection and/or radiotherapy). The HPG axis is particularly sensitive to the suppressive effects of hyperprolactinaemia that can occur for many reasons, including prolactinomas, and as a side effect of certain drug therapies. Physiologically, prolactin (combined with the suppressive effects of autonomic neural signals from suckling) plays a key role in suppressing the gonadal axis and establishing temporary CH during lactation. Leptin is a further key endocrine regulator of the HPG axis. During starvation, hypoleptinaemia (from diminished fat stores) results in activation of hypothalamic agouti-related peptide neurons that have a dual purpose to enhance appetite (important for survival) and concomitantly suppresses GnRH neurons via effects on neural kisspeptin release. Obesity is associated with hyperleptinaemia and leptin resistance that may also suppress the HPG axis. The suppressibility of the HPG axis also leaves it vulnerable to the effects of external signals that include morphine, anabolic-androgenic steroids, physical trauma and stress, all of which are relatively common causes of CH. Finally, the HPG axis is susceptible to congenital malformations, with reports of mutations within >50 genes that manifest with congenital CH, including Kallmann Syndrome associated with hyposmia or anosmia (reduction or loss of the sense of smell due to the closely associated migration of GnRH with olfactory neurons during embryogenesis). Analogous to the HPG axis itself, patients with CH are often vulnerable, and their clinical management requires both sensitivity and empathy.

scholarly journals Sex in the brain: How the brain regulates reproductive function

2009 ◽  
Vol 31 (2) ◽  
pp. 4-7 ◽  
Author(s):  
Manuel Tena-Sempere ◽  
Ilpo Huhtaniemi
Keyword(s):  
Hierarchical Control ◽  
Reproductive Function ◽  
Neural Cells ◽  
Hpg Axis ◽  
Functional Balance ◽  
Regulatory Systems ◽  
Recent Developments ◽  
Puberty Onset ◽  
G Protein Coupled ◽  
The Brain

Reproductive functions are maintained by a complex hormonal regulatory network called the hypothalamic–pituitary–gonadal (HPG) axis, which is under the hierarchical control of a network of neurohormones that ultimately modulate the synthesis and pulsatile release of the decapeptide gonadotropin-releasing hormone (GnRH) by specialized neural cells distributed along the mediobasal hypothalamus. This neuropeptide drives the production of the two gonadotropic hormones of the anterior pituitary gland, luteinizing hormone (LH) and folliclestimulating hormone (FSH), which are released into the circulation and regulate specific functions of the ovary and testis. In turn, hormones produced by the gonads feed back to the hypothalamic– pituitary level to maintain functional balance of the HPG axis, through negative and positive (only in females) regulatory loops. In this article, we review the main hormonal regulatory systems that are operative in the HPG axis with special emphasis on recent developments in our knowledge of the neuroendocrine pathways governing GnRH secretion, including the identification of kisspeptins and G-protein-coupled receptor 54 (GPR54) as major gatekeepers of puberty onset and fertility.

The relation between obesity, kisspeptin, leptin, and male fertility

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Saber Ghaderpour ◽  
Rafighe Ghiasi ◽  
Hamed Heydari ◽  
Rana Keyhanmanesh
Keyword(s):  
Male Fertility ◽  
Sperm Quality ◽  
Reproductive Potential ◽  
Reproductive Function ◽  
Leptin Resistance ◽  
Resistance Development ◽  
Reproductive Axis ◽  
Gnrh Release ◽  
Hpt Axis ◽  
The Relationship

Abstract Over the past decades, obesity and infertility in men increased in parallel, and the association between both phenomena have been examined by several researchers. despite the fact that there is no agreement, obesity appears to affect the reproductive potential of men through various mechanisms, such as changes in the hypothalamic-pituitary-testicular (HPT) axis, spermatogenesis, sperm quality and/or alteration of sexual health. Leptin is a hormone produced by the adipose tissue, and its production elevates with increasing body fat. Many studies have supported the relationship between raised leptin production and reproductive function regulation. In fact, Leptin acts on the HPT axis in men at all levels. However, most obese men are insensitive to increased production of endogenous leptin and functional leptin resistance development. Recently, it has been recommended that Kisspeptin neurons mediate the leptin’s effects on the reproductive system. Kisspeptin binding to its receptor on gonadotropin-releasing hormone (GnRH) neurons, activates the mammal’s reproductive axis and stimulates GnRH release. Increasing infertility associated with obesity is probably mediated by the Kisspeptin-GnRH pathway. In this review, the link between obesity, kisspeptin, leptin, and male fertility will be discussed.

scholarly journals Hypothalamic action of phoenixin to control reproductive hormone secretion in females: importance of the orphan G protein-coupled receptor Gpr173

2016 ◽  
Vol 311 (3) ◽  
pp. R489-R496 ◽  
Author(s):  
Lauren M. Stein ◽  
Chloe W. Tullock ◽  
Stacy K. Mathews ◽  
David Garcia-Galiano ◽  
Carol F. Elias ◽  
...  
Keyword(s):  
G Protein ◽  
Hormone Secretion ◽  
Reproductive Function ◽  
Female Rats ◽  
Pituitary Cells ◽  
G Protein Coupled Receptor ◽  
Hpg Axis ◽  
Ovarian Cyclicity ◽  
Lh Secretion ◽  
G Protein Coupled

Sexual maturation and maintenance of reproductive function are regulated by neurohormonal communication between the hypothalamus, pituitary, and gonads (referred to as the HPG axis). Phoenixin (PNX) is a newly identified, endogenous peptide abundantly produced in the hypothalamus and shown to be an important mediator of ovarian cyclicity. However, the underlying mechanisms by which phoenixin functions within the HPG axis are unknown. Previous in vitro studies demonstrated a direct action of PNX on gonadotrophs to potentiate gonadotrophin-releasing hormone (GnRH) induced luteinizing hormone (LH) secretion. Therefore, we hypothesized that centrally derived phoenixin regulates the preovulatory LH surge required for ovarian cyclicity. We observed a significant dose-related increase in the level of plasma LH in diestrous, female rats that were given an intracerebroventricular injection of PNX compared with vehicle-treated controls. While this suggests that even under low-estrogen conditions, PNX acts centrally to stimulate the HPG axis, further characterization is contingent on the elucidation of its cognate receptor. Using the “deductive ligand receptor matching strategy,” we identified the orphan G protein-coupled receptor, Gpr173, as our top candidate. In cultured pituitary cells, siRNA-targeted compromise of Gpr173 abrogated PNX's action to potentiate GnRH-stimulated LH secretion. In addition, siRNA-mediated knockdown of endogenous Gpr173, which localized to several hypothalamic sites related to reproductive function, not only significantly extended the estrous cycle but also prevented the PNX-induced LH secretion in diestrous, female rats. These studies are the first to demonstrate a functional relationship between PNX and Gpr173 in reproductive physiology and identify a potential therapeutic target for ovulatory dysfunction.

scholarly journals Leptin and Obesity: Role and Clinical Implication

2021 ◽  
Vol 12 ◽  
Author(s):  
Milan Obradovic ◽  
Emina Sudar-Milovanovic ◽  
Sanja Soskic ◽  
Magbubah Essack ◽  
Swati Arya ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Body Mass ◽  
Animal Studies ◽  
Leptin Receptor ◽  
Reproductive Function ◽  
Peptide Hormone ◽  
Feedback Mechanism ◽  
Leptin Resistance ◽  
Total Body Mass ◽  
Negative Feedback Mechanism

The peptide hormone leptin regulates food intake, body mass, and reproductive function and plays a role in fetal growth, proinflammatory immune responses, angiogenesis and lipolysis. Leptin is a product of the obese (ob) gene and, following synthesis and secretion from fat cells in white adipose tissue, binds to and activates its cognate receptor, the leptin receptor (LEP-R). LEP-R distribution facilitates leptin’s pleiotropic effects, playing a crucial role in regulating body mass via a negative feedback mechanism between adipose tissue and the hypothalamus. Leptin resistance is characterized by reduced satiety, over-consumption of nutrients, and increased total body mass. Often this leads to obesity, which reduces the effectiveness of using exogenous leptin as a therapeutic agent. Thus, combining leptin therapies with leptin sensitizers may help overcome such resistance and, consequently, obesity. This review examines recent data obtained from human and animal studies related to leptin, its role in obesity, and its usefulness in obesity treatment.

scholarly journals A Mouse Model of Shiftwork Reveals Sex-Specific Impairments in Circadian Behavior and Reproductive Tissue Timekeeping

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A530-A531
Author(s):  
Alexandra M Yaw ◽  
Autumn Mclane-Svoboda ◽  
Duong Nguyen ◽  
Thu Van Quynh Duong ◽  
Hanne Mette Hoffmann
Keyword(s):  
Circadian Rhythms ◽  
Wheel Running ◽  
Reproductive Function ◽  
Tissue Level ◽  
The Body ◽  
Luciferase Reporter ◽  
Light At Night ◽  
Hpg Axis ◽  
Circadian Phase ◽  
Strong Body

Abstract Approximately 21 million Americans are employed in nighttime or rotating shiftwork, which is linked with numerous health risks, including reduced reproductive success. While there is a strong body of clinical evidence associating shift workers with deficits in fertility, very little is known about the mechanisms by which shiftwork produces reproductive dysfunction. One important feature of shiftwork is extensive exposure to light at night. Light is one of the strongest timing cues for the circadian system, where exposure to mistimed light (light at night) can disrupt timekeeping throughout the body, leading to a mistiming of physiological processes and resulting in disease development. Our goal is to determine if a light-based model of rotating shiftwork (shift-light), composed of an alternating 6 hour phase advance or delay every 4 days for 5-10 weeks, disrupts circadian rhythms in the reproductive hypothalamic-pituitary-gonadal (HPG) axis, leading to mis-timed tissue rhythms and reduced fertility. We hypothesize that shift-light disrupts wheel running behavior and underlying cellular circadian rhythms in the HPG axis, resulting in reduced reproductive function. Using the validated circadian Per2:luciferase reporter mice, we assessed wheel-running behavior and Per2:luciferase rhythms in tissue explants from males and females. Behavioral data revealed that both sexes adapt their wheel running to shift-light paradigm; however, females, but not males, displayed a significant deficit in their ability to entrain to phase advances following 4 shifts. This sex-specific disruption was supported by preliminary tissue explant Per2:luciferase rhythms, which suggest that shift-light alters tissue level circadian phase synchrony in female, but not male, HPG axis tissues. Importantly, females exhibited shortened estrous cycling during shift-light, suggesting the altered HPG axis synchrony could be directly impacting reproductive function. We are currently working to extend this work to determine how this desynchrony impacts hormone release, including luteinizing hormone and follicle stimulating hormone. Together, this work provides insight into how shiftwork may influence circadian rhythms in reproductive tissues and suggests that females may have increased vulnerability to reproductive deficits from shiftwork.

scholarly journals Prolactin maintains parental responses and alters reproductive axis gene expression, but not courtship behaviors, in both sexes of a biparental bird

2021 ◽  
Author(s):  
Victoria S Farrar ◽  
Laura Flores ◽  
Rechelle C Viernes ◽  
Laura Ornelas Pereira ◽  
Susan Mushtari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parental Care ◽  
Hormone Receptor ◽  
Reproductive Function ◽  
Columba Livia ◽  
Receptor Expression ◽  
Hpg Axis ◽  
Reproductive Behaviors ◽  
Courtship Behaviors ◽  
Parental Responses

Prolactin, a hormone involved in vertebrate parental care, is hypothesized to inhibit reproductive hypothalamic-pituitary-gonadal (HPG) axis activity during parenting, thus maintaining investment in the current brood as opposed to new reproductive efforts. While prolactin underlies many parental behaviors in birds, its effects on other reproductive behaviors, such as courtship, remain unstudied. How prolactin affects neuropeptide and hormone receptor expression across the avian HPG axis also remains unknown. To address these questions, we administered ovine prolactin (oPRL) or a vehicle control to both sexes in experienced pairs of the biparental rock dove (Columba livia), after nest removal at the end of incubation. We found that oPRL promoted parental responses to novel chicks and stimulated crop growth compared to controls, consistent with other studies. However, we found that neither courtship behaviors, copulation rates nor pair maintenance differed with oPRL treatment. Across the HPG, we found oPRL had little effect on gene expression in hypothalamic nuclei, but increased expression of FSHB and hypothalamic hormone receptor genes in the pituitary. In the gonads, oPRL increased testes size and gonadotropin receptor expression, but did not affect ovarian state or small white follicle gene expression. However, the oviducts of oPRL-treated females were smaller and had lower estrogen receptor expression compared with controls. Our results highlight that some species, especially those that show multiple brooding, may be able to maintain mating behavior despite elevated prolactin. Thus, mechanisms may exist for prolactin to promote investment in parental care without concurrent inhibition of reproductive function or HPG axis activity.

Evaluation of Infertility

2018 ◽  
Author(s):  
Jessica R Zolton ◽  
Alan H. DeCherney
Keyword(s):  
Semen Analysis ◽  
Reproductive Function ◽  
Antral Follicle ◽  
Antral Follicle Count ◽  
World Health ◽  
Male Factor ◽  
Tubal Patency ◽  
Ovulatory Dysfunction ◽  
Common Causes ◽  
Health Organization

In 2009, the World Health Organization formally recognized infertility as a disease of the reproductive system. This designation serves to ease access to infertility evaluation and treatment. Infertility is a disease of both men and women, and proper evaluation of both partners is necessary. Common causes of infertility are ovulatory dysfunction, tubal and pelvic pathology, unexplained infertility, and male factor. A complete history and physical examination may uncover the underlying etiology, although verification of tubal patency and normal semen analysis is warranted. This period also offers an opportunity to perform preconception testing and optimize women’s health before conception. Treatment for infertility is aimed to restore normal reproductive function and anatomy. In addition, patient education and counseling is indeed a very important aspect of infertility care. This review contains 5 figures, 5 tables and 60 references Key Words: anovulation, Antimullerian hormone, antral follicle count, hysterosalpingogram, infertility, infertility evaluation, ovarian reserve testing, polycystic ovarian syndrome, saline infusion sonohysterography

Role of RF-amid Related Peptide-3 (RFRP-3) in Inhibitory Effect of Orexin A on Reproductive Function in the Animal Model of Male Wistar Rats

2019 ◽  
Vol 127 (10) ◽  
pp. 697-705 ◽  
Author(s):  
Jafar Alipoor Hefshejanni ◽  
Homayoun Khazali
Keyword(s):  
Third Ventricle ◽  
Reproductive Function ◽  
Inhibitory Effect ◽  
Male Rats ◽  
Orexin A ◽  
Hpg Axis ◽  
Related Peptide ◽  
Male Wistar Rats ◽  
Novel Target ◽  
The Impact

Abstract Aims The aim of the present study is to examine the orexin A (OXA) signaling can leave any impact on the hypothalamic-pituitary-gonadal (HPG) axis and this impact can be relayed through the pathway of RF amide-related peptide-3 (RFRP-3, the mammalian ortholog of the avian gonadotropin-inhibitory hormone)/G-protein coupled receptor (GPR)-147 (RFRP-3 receptor) as a novel target for controlling of HPG axis in the male rats. Materials and Methods Male rats were categorized randomly into experimental groups including control vehicle, OXA, and its antagonists’ group and went through to surgical cannulation into the third ventricle. After the intracerebroventricular injection of each solution, blood samples were collected for measurements of the LH and testosterone using radioimmunoassay method. Hypothalamus of the animals were isolated for analysis of the relative expression of Rfrp-3/Gpr-147 along with Gnrh gene by Real time-PCR. Also, in the different cohort of animal sexual behavior test was done. Results It was shown that OXA significantly decreases the mean serum level of the LH and testosterone and, at the same time, its antagonists neutralize this impact. Moreover, we demonstrated that OXA has reduced the hypothalamic gene expression of Gnrh and increased the expression of Rfrp-3 and Gpr-147 genes. While OXA antagonists neutralize this impact. Conclusions The results of this study are related to the impact of orexin on the HPG axis. It is recommended that RFRP-3/GPR-147 system as the interneural pathway relay the data of orexin to the neurons of GnRH.

Hormonal regulation of reproduction and the antler cycle in the male Columbian black-tailed deer (Odocoileus hemionus columbianus). Part II. The effects of methallibure and hormone treatment

1976 ◽  
Vol 54 (10) ◽  
pp. 1637-1656 ◽  
Author(s):  
Nels O. West ◽  
H. C. Nordan
Keyword(s):  
Hormonal Regulation ◽  
Reproductive Function ◽  
Hormone Treatment ◽  
Odocoileus Hemionus Columbianus ◽  
Hormonal Stimulation ◽  
Testosterone Production ◽  
Antler Growth ◽  
Gonadotrophin Secretion ◽  
Normal Period ◽  
Androgenic Steroids

Methallibure, a non-steroidal inhibitor of gonadotrophin secretion, arrested antler growth and suppressed reproduction. The administration of prolactin, pregnant mares' serum gonadotrophin (PMS), and some androgenic steroids to methallibure-treated deer during June and July failed to stimulate antler growth, but human chorionic gonadotrophin (HCG) did rejuvenate it in one instance. None of these hormones was effective in completely restoring reproductive function, although PMS and HCG were capable of stimulating the production of enough testosterone to induce velvet shedding.During the normal period of antler growth, the testes of methallibure-treated deer did not respond to the exogenous administration of HCG by secreting testosterone, whereas both PMS and prolactin were effective in this respect. After the administration of PMS, HCG was capable of stimulating testosterone production, but it was ineffective in the deer previously treated with prolactin. Also, when methallibure treatment was terminated in the fall, testosterone production and spermatogenesis recovered, but the deer that had previously received prolactin did not produce mature sperm until the next spring. Thus, the testicular response may depend on the temporal sequence as well as on the type of hormonal stimulation. The results of this study support the hypothesis that a gonadotrophin is responsible for stimulating antler growth.

scholarly journals Congenital hypogonadotropic hypogonadism: from clinical characteristics to genetic aspects

2021 ◽  
Vol 5 (3) ◽  
pp. 97-105
Author(s):  
Ahreum Kwon ◽  
Ho-Seong Kim
Keyword(s):  
Clinical Characteristics ◽  
Pubertal Development ◽  
Hypogonadotropic Hypogonadism ◽  
Reproductive Function ◽  
Delayed Puberty ◽  
Activation Process ◽  
Hpg Axis ◽  
Congenital Hypogonadotropic Hypogonadism ◽  
Sexual Characteristics ◽  
Main Component

Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder caused by a deficiency in gonadotropin-releasing hormone (GnRH). CHH is characterized by delayed puberty and/or infertility; this is because GnRH is the main component of the hypothalamic-pituitary-gonadal (HPG) axis, which is a key factor in pubertal development and reproductive function completion. However, since the development of sexual characteristics and reproduction begins in the prenatal period and is very complex and delicate, the clinical characteristics and involved genes are very diverse. In particular, the HPG axis is activated three times in a lifetime, and the symptoms and biochemical findings of CHH vary by period. In addition, related genes also vary according to the formation and activation process of the HPG axis. In this review, the clinical characteristics and treatment of CHH according to HPG axis activation and different developmental periods are reviewed, and the related genes are summarized according to their pathological mechanisms.

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