Kisspeptin and the regulation of the hypothalamic-pituitary-gonadal axis in the rhesus monkey (Macaca mulatta)

The present article reviews recent studies of monkeys and, in some cases, humans that have been conducted to examine the role of kisspeptin-GPR54 signaling in the regulation of the hypothalamic-pituitary-gonadal axis in higher primates. This area of peptide biology was initiated in 2003 by the discovery that loss of function mutations of GPR54 in man were associated with hypogonadotropic hypogonadism and absent or delayed puberty. Puberty in the monkey, an experimental model commonly used to study this fundamental developmental stage, is first described. This is followed by a review of the role of kisspeptin in the regulation of the postnatal ontogeny of GnRH pulsatility. The roles of kisspeptin in GnRH pulse generation and in the feedback loops governing gonadotropin secretion in primates are then discussed. A brief section on kisspeptin-GPR54 signaling at the pituitary and gonadal levels is also included. The review concludes with a discussion of the phenomenon of GPR54 downregulation by continuous exposure to kisspeptin and its therapeutic implications.     

Mandibular growth in the rhesus monkey (Macaca mulatta)

Mandibular growth of 42 rhesus monkeys (Macaca mulatta) was analyzed quantitatively and qualitatively. Four groups of animals were defined according to dentitional age (i.e., infant, juvenile, adolescent, young adult). At each age growth was observed for a 24 week period. Since some animals were observed at more than one stage of development, 57 periods of growth were studied. The growth incremental data were collected by superimposing serial cephalograms on mandibular implants. Growth and remodeling of both the skeletal and dento-alveolar components of the rhesus mandible were greatest in the infant monkeys and were less in successive age groups. Posterior relocation of the ramus was noted in all age groups while bone deposition on the anterior and inferior borders of the mandibular body was greatest in the younger animals. The most pronounced dental changes also occurred in the younger animals while the dentitions of the adolescent and adult animals were generally more stable. This study demonstrates that the rate and direction of normal mandibular growth varies with the age of the animal. Furthermore, mandibular growth is quantified at four defined maturational levels to provide a set of values illustrating normal mandibular growth. These values can also be used as control data for experimental studies.     

Corneal biometrics of the rhesus monkey (Macaca mulatta)

Keratometry, retinoscopy, horizontal diameter, and pachymetry were measured in adult and infant rhesus monkeys (Macaca mulatta). The adult monkeys had a mean corneal thickness of 0.47 +/- 0.03 mm (+/- standard deviation), corneal diameters of 10.6 +/- 0.5 mm, keratometry values of 51.90 +/- 1.61 diopters, and subjective refractions of 0.48 +/- 2.36 diopters. Female adult monkeys had smaller corneal diameters by 0.06 mm (P = .02) and steeper corneas by 0.77 diopters (P = .04). Infant female monkeys also had steeper corneas by 2.37 diopters (P = .05). No significant differences were found between right and left eyes in either adult or infant monkeys.     

Oxytocin and pair compatibility in adult male rhesus macaques (Macaca mulatta)

Pair housing is considered one of the best ways of promoting psychological wellbeing for caged macaques. However, incompatible partnerships can result in stress or aggression. Though previous studies have analyzed the role of variables such as age, weight, gender, and temperament on pair compatibility, few have examined the relationship between physiological parameters and pair compatibility. Oxytocin is known to promote prosocial nonsexual behavior in various primate species and may serve as an indicator of pair compatibility. In this study, we examined the association between peripheral oxytocin levels and prosocial behaviors in isosexual pairs of male rhesus macaques. We hypothesized that animals that demonstrated high levels of prosocial behaviors would have higher oxytocin levels than those showing low levels of the behavior. In addition, to elucidate the relationship between oxytocin and compatibility, we compared peripheral oxytocin between the highly affiliative animals and single‐housed males identified as having multiple unsuccessful pair attempts with multiple partners. We collected plasma oxytocin on 40 pairs of monkeys that had lived together for at least 1 month and 20 single‐housed animals. Further, we simultaneously collected behavioral data on the pairs, recording prosocial interactions (e.g., groom, play). Oxytocin varied among individuals, but was highly correlated between members of a pair (r = 0.58, p < .001). Additionally, prosocial behavior was positively correlated with plasma oxytocin (r = 0.38, p < .02). However, contrary to our expectations, oxytocin did not differ between single and highly affiliative pair‐housed animals (F_(1,38) = 0.71, p = .40). Our results suggest that oxytocin may be associated with the quality of isosexual pairs of male macaques. More work is needed to determine the nature of this relationship.     

Conjoined twins in a rhesus monkey (Macaca mulatta)

Conjoined twinning is an extremely rare occurrence among human and nonhuman primates. The current report describes a case of minimally conjoined omphalopagus rhesus monkey twins that were observed in the breeding colony at the California Regional Primate Research Center. The full-term nonviable male twins were morphologically normal and united in the umbilical region, involving the liver, xiphoid, umbilicus, body wall, and skin. The umbilical cords were separate, but closely aligned, within an ensheathing amnion; each cord contained two arteries and a vein. The closely associated cords were centrally inserted on a large bidiscoid placenta. There were no gross or histologic abnormalities in the viscera, with the exception of enlargement of the left central liver lobes, which constituted the area of attachment. The cause of death was attributed to asphyxia and trauma experienced during parturition.     

Arteriovenous malformation in a rhesus monkey (Macaca mulatta)

A developmental arteriovenous malformation of the right arm was recognized in a 1-year-old rhesus monkey. The diagnosis was based on physical findings, ultrasound, and angiography. Treatment consisting of therapeutic transcatheter embolization using polyvinyl alcohol was performed with partial success. Necropsy revealed a lesion that was limited to the skin and subcutis. An abnormal vascular pattern was present leading to and within the lesion.     

Alopecia areata in a rhesus monkey (Macaca mulatta)

BACKGROUND: A 14-year-old female rhesus monkey (Macaca mulatta) of Chinese origin has been suffering from alopecia universalis since childhood. METHODS: Recently, the health status of the animal was recorded comprehensively by detailed clinical examination including hematology and serology supplemented by histological and immunohistochemical investigations of skin biopsies and molecular biological techniques to clarify the causes of the persistent hair loss. RESULTS AND CONCLUSIONS: The hairless gene (hr) nonsense mutation was ruled out by polymerase chain reaction and by sequencing of the corresponding gene. Histological examinations revealed a prominent chronic lymphocytic perifolliculitis and folliculitis affecting anagen stage hair follicles as well as miniaturized hair follicles. Immunohistochemistry using the antibodies CD3, CD20 and CD4 confirmed the diagnosis of a T-cell-mediated autoimmune disease resembling alopecia areata universalis in humans.     

Sociability and responses to video playbacks in adult male rhesus monkeys (Macaca mulatta)

Studies of several primate species have suggested the existence of a personality dimension typically labeled ‘Sociability,’ which reflects an animal’s tendency to interact with others. The hypothesis that Sociability is related to social skill was tested in the present study by exposing six high- and six low-Sociable adult male rhesus macaques to videotaped presentations of unfamiliar males displaying aggressive or affiliative behaviors. Low-Sociable animals displayed higher frequencies of yawn, lower activity and tended to have higher durations of watching during the presentations that displayed social signals, and significantly fewer lipsmacks to presentations that depicted no social behavior. In response to viewing threats, tooth-grinds, yawns, and lipsmacks, both low- and high-Sociable animals’ most frequent response was to gaze avert; low-Sociable animals, however, had nearly twice the latency to gaze avert than did high-Sociable animals. The low-Sociable animals’ greater tendency to ‘sit and stare’ during the videotaped playbacks suggests that low-Sociable animals have poorer social skills. The possible developmental origins of variation in Sociability, and the functional consequences of such variation for survival and reproduction are discussed.     

Oxytocin is luteolytic in the rhesus monkey (Macaca mulatta)

Oxytocin (10 mi.u./microliter/h) or vehicle (0.5% chlorobutanol in saline, 1 microliter/h) was chronically infused directly into the corpus luteum of normally cyclic rhesus monkeys, by means of an Alzet pump-ovarian cannula system. Infusion of oxytocin (N = 6) or vehicle (N = 5) began 6 days after the preovulatory oestradiol surge, and daily peripheral blood samples were taken. Oxytocin caused a significant (P less than 0.05) decrease in progesterone, beginning 1 day after treatment, and oestradiol after 4 days; progesterone and oestradiol remained significantly depressed until menstruation. However, peripheral LH concentrations remained unchanged. The duration of the luteal phase, menstrual cycle and the onset of menses from the initiation of oxytocin infusion were significantly (P less than 0.01) shorter when compared to those of vehicle-treated controls. These results show that oxytocin can induce functional luteolysis in the primate and supports the hypothesis that oxytocin of luteal origin may play a role in spontaneous luteolysis.     

Studies of rhesus monkey (Macaca mulatta) hemoglobin.

One hemaglobin was found in the adult rhesus monkey (Macaca mulatta) by the technique of isoelectric focusing. In addition to the adult hemoglobin, one fetal hemaglobin was observed in neonates of the same species. The alpha and non-alpha globins of rhesus monkey hemoglobins showed similar electrophoretic mobilities as those of human hemoglobin A by cellulose acetate membrane electrophoresis. It appeared that the rhesus monkey hemoglobin system is a good model system for the study of human hemoglobin development.     

Cholelithiasis in a male rhesus monkey (Macaca mulatta) fed a cholesterol-containing diet.

In this report we describe the development of cholelithiasis in a male rhesus monkey fed a cholesterol-containing diet for 24 months. This represents the only case of cholelithiasis in this species of nonhuman primate that we have observed out of a population of over 500 rhesus monkeys fed similar cholesterol-containing diets. Associated with the appearance of gallstones was the production of bile saturated with cholesterol, and the excretion of bile with an abnormal bile acid composition.     

Seasonal influences on rhesus monkey (Macaca mulatta) behavior

Seasonal differences in the behavior of 2.5- to 4.5-year-old female subjects and male subjects >2.5 years of age were studied in two rhesus monkey groups over a period of 6 years. The frequencies and durations of sexual acts and states were higher during the Fall in Georgia, USA, but were significant only with regard to female partners. Total time in social proximity, scores for proximity by partner without social interaction, nonspecific contact, grooming received, and noncontact forms of aggression with female partners were also higher in the Fall. Although more submission and agonistically ambiguous responses were received from female partners during the Fall, no seasonal pattern prevailed for responses performed. More contact aggression was directed to males in the Spring, and the pattern of agonistic behavior observed cannot be accounted for by males fighting over estrous females. Significantly more play was observed among subjects in the Fall, but the oldest males played more in the Spring. Some patterns, like huddling, were seen more in the Fall, but they may have been due to temperature differences. Seasonal differences in morphology and behavior cannot be attributed to a single variable, like temperature, level of gonadal hormones, or sexual competition, and may reflect a broader adaptation to seasonal variables.     

Taste sensitivity to phenylthiourea (PTC) in the rhesus monkey (Macaca mulatta)

The hypothesis that the distribution of thresholds of taste sensitivity to phenylthiourea (PTC) is unimodal was tested in a group of 367 rhesus monkeys. The distribution was found to be unimodal and highly skewed. The regression of taste thresholds of offspring on that of their father was 0.840±0.34. This estimate is consistent with an hypothesis of essentially no environmental influence. It was concluded that phenotypic variability at the PTC tasting locus in rhesus monkeys is almost totally determined by the non-additive influences of several genes on taste sensitivity.     

Sex differences in adolescent rhesus monkey (Macaca mulatta) Behavior

Sex differences in the behavior of 2.5- to 4.5-year-old rhesus monkeys, living in two social groups approximating natural compositions, were studied over a period of 3 years. Both sexes interacted significantly more often with members of their own sex in agonistic and affiliative interactions even when total rates and durations for male and female subjects did not differ. Strong sexual segregation was also seen in proximity, nonspecific contact, and huddling partners. Males were more involved in play and sex than were females and engaged in these activities primarily with other males. Females did more grooming than males, but groomed both male and female partners. Females also appeared to interact with a wider age range of partners than did males. Although total participation in aggressive interactions did not differ between the two sexes, females used more active forms of agonistic expression than did males. These differences in the behavior of adolescent rhesus are hypothesized to lead to social bonding among adolescent males, while females remain bonded to their matri-lines, including younger males and some fully adult males associated with matrilineal relatives. Adolescent males emigrate from their natal groups but retain sociality and bond to males and females in new groups as they become adult. © 1993 Wiley-Liss, Inc.     

Persistent truncus arteriosus in a rhesus monkey (Macaca mulatta)

A 47-day-old female rhesus macaque (Macaca mulatta) was examined because of a severe holosystolic heart murmur (grade 5/6) and signs of congestive heart failure. Results of physical examination, thoracic radiography, and cardiac ultrasonography confirmed an advanced stage of congestive heart failure. Due to the animal's age and clinical signs of disease, a congenital heart defect was suspected. Necropsy revealed a rare congenital heart defect known as persistent (common) truncus arteriosus.     

Sebaceous gland adenoma in a rhesus monkey (Macaca mulatta)

A tumor mass was identified below the shoulder region of a 5-year-old male rhesus monkey (Macaca mulatta). The mass was excised and diagnosed as sebaceous gland adenoma based on the microscopic findings. Morphologically it appeared as an elevated, dome-shaped, circumscribed mass of 3.6 x 2.8 x 3.2 cm in dimension with tan speckled color. Histologically, the tumor was composed of mature, sebaceous cells (sebocytes), basal cells arranged in a mass of irregular shapes and sizes, with a characteristic appearance of poly or multilobular structure. Sebocytes were well differentiated with foamy cytoplasm in the center of the lobules and poorly or undifferentiated densely staining basal cells in the periphery of the lobules. Cellular changes in the adjacent lymph node included hyperplasia of plasma cells, macrophages and lymphoid elements with typical mitosis.     

Adenoviral hepatitis in a SIV-infected rhesus monkey (Macaca mulatta)

BACKGROUND: A 5-year-old female rhesus monkey infected with simian immunodeficiency virus became clinically suspicious with anorexia, increasing weakness and apathy eighty-five weeks after the tonsillar virus inoculation and was euthanised due to a poor prognosis. METHODS AND RESULTS: Postmortal examinations revealed a severe multifocal to coalescing necotizing hepatitis with numerous intranuclear basophilic inclusion bodies. Transmission electron microscopy of the liver resulted in the finding of adenovirus like particles arranged in paracrystalline arrays within the nuclei of hepatocytes.CONCLUSION: The SIV infected rhesus monkey suffered from an adenovirus included necortizing hepatitis, an extremely rare organ manifestation of adenovirus infection in nonhuman primates.