Puberty and growth rate in thoroughbred fillies

We measured progesterone and estradiol levels from birth to the beginning of adult life in 10 Thoroughbred fillies from the Equilia Stud Farm in Avaré SP, Brasil. The animals were measured and weighed monthly for the determination of body development and of a possible correlation between the rate of weight and height gain and the onset of detectable sex hormone levels. Jugular blood was collected twice a week and stored at -20 degrees C until assay of progesterone by a solid phase RIA with a sensitivity of 0.32 nmol L and of estradiol by liquid phase RIA adapted to low levels (3.67 pmol L ). The fillies were born with high serum levels of both hormones, which fell to undetectable levels by the first week of life. A variation in growth rate was observed, with the highest levels occurring from birth to the 3rd month of life, followed by a reduction until 15 mo of life, when fast growth was resumed. The monthly weight gain was 1.5% when the fillies reached puberty and 5.4% during the next month, (P < 0.05, Friedman test). During this second period of accelerated growth after the beginning of progesterone production at detectable levels (above 0.318 nmol L ), the parameters of skeletal growth did not differ (P > 0.05). The month of onset of puberty was the month of lowest weight gain in the life of the fillies, and it coincided with the highest insolation period. In conclusion, horses, like all other developed vertebrates, have a double pattern of development, with the acceleration observed at puberty depending on sex steroids, which in turn coincides with the highest insolation period. Gonadal activity characterized by serum progesterone levels was low from birth to the onset of puberty. After puberty the progesterone cycles were similar to those of adult animals with a mature hypothalamic-gonadal axis.     

Lineage-specific restraint of pituitary gonadotroph cell adenoma growth

Although pituitary adenomas are usually benign, unique trophic mechanisms restraining cell proliferation are unclear. As GH-secreting adenomas are associated with p53/p21-dependent senescence, we tested mechanisms constraining non-functioning pituitary adenoma growth. Thirty six gonadotroph-derived non-functioning pituitary adenomas all exhibited DNA damage, but undetectable p21 expression. However, these adenomas all expressed p16, and >90% abundantly expressed cytoplasmic clusterin associated with induction of the Cdk inhibitor p15 in 70% of gonadotroph and in 26% of somatotroph lineage adenomas (p = 0.006). Murine LβT2 and αT3 gonadotroph pituitary cells, and αGSU.PTTG transgenic mice with targeted gonadotroph cell adenomas also abundantly expressed clusterin and exhibited features of oncogene-induced senescence as evidenced by C/EBPβ and C/EBPδ induction. In turn, C/EBPs activated the clusterin promoter ～5 fold, and elevated clusterin subsequently elicited p15 and p16 expression, acting to arrest murine gonadotroph cell proliferation. In contrast, specific clusterin suppression by RNAis enhanced gonadotroph proliferation. FOXL2, a tissue-specific gonadotroph lineage factor, also induced the clusterin promoter ～3 fold in αT3 pituitary cells. As nine of 12 pituitary carcinomas were devoid of clusterin expression, this protein may limit proliferation of benign adenomatous pituitary cells. These results point to lineage-specific pathways restricting uncontrolled murine and human pituitary gonadotroph adenoma cell growth.     

Behavioral despair in mice after prenatal stress

Maternal stress during pregnancy produced behavioral alterations in both sexes with regard to sexual behavior, aggressive, maternal, lateralization and depression. In the present paper, sex differences for depression in mice was studied. No sex differences between female and male mice groups were observed either in swimming-induced immobility or in the open-field test (ambulation, rearing and boluses). Prenatal stress produced: 1) an increase of immobility time in female mice for swimming-induced immobility, but not in male mice; 2) an increase of ambulation in female mice for open-field test, but not in male mice; 3) there were no significant differences in rearing and boluses between stress and control groups either for female or male mice. Prenatal stress increases the risk of depression and locomotor activity in adult female mice.     

Puberty and adolescent sexuality

This article is part of a Special Issue “Puberty and Adolescence”.     

Disentangling prenatal and postnatal maternal genetic effects reveals persistent prenatal effects on offspring growth in mice

Mothers are often the most important determinant of traits expressed by their offspring. These "maternal effects" (MEs) are especially crucial in early development, but can also persist into adulthood. They have been shown to play a role in a diversity of evolutionary and ecological processes, especially when genetically based. Although the importance of MEs is becoming widely appreciated, we know little about their underlying genetic basis. We address the dearth of genetic data by providing a simple approach, using combined genotype information from parents and offspring, to identify "maternal genetic effects" (MGEs) contributing to natural variation in complex traits. Combined with experimental cross-fostering, our approach also allows for the separation of pre- and postnatal MGEs, providing rare insights into prenatal effects. Applying this approach to an experimental mouse population, we identified 13 ME loci affecting body weight, most of which (12/13) exhibited prenatal effects, and nearly half (6/13) exhibiting postnatal effects. MGEs contributed more to variation in body weight than the direct effects of the offsprings' own genotypes until mice reached adulthood, but continued to represent a major component of variation through adulthood. Prenatal effects always contributed more variation than postnatal effects, especially for those effects that persisted into adulthood. These results suggest that MGEs may be an important component of genetic architecture that is generally overlooked in studies focused on direct mapping from genotype to phenotype. Our approach can be used in both experimental and natural populations, providing a widely practicable means of expanding our understanding of MGEs.     

Puberty and psychological development

Emphasis is placed on the body and its role in shaping our relationship to reality. Puberty is responsible for integrating an irreversible body image either masculine or feminine. Pubertal pathology in which the fantasies about physical bisexuality remain ensconced can make working through psychical bisexuality a more arduous task.     

Intrathymic T cell repertoire after prenatal trinitrobenzene-sulfonic acid-treatment

It is still a matter of debate, whether tolerance toward self-non-MHC antigens is due to intrathymic deletion or to regulatory processes in the periphery. To further pursue this question, responsiveness toward TNP and an anti-TNP monoclonal antibody (Sp6) carrying a recurrent idiotype was evaluated in prenatally trinitrobenzenesulfonic acid (TNBS)-treated mice. In prenatally untreated as well as in TNBS-treated mice, thymocytes proliferating in the absence of nominal antigen were double negative (L3T4-/Lyt2-), but antigen-specific thymocytes were single positive (L3T4+/Lyt2- or L3T4-/Lyt2+). TNBS-treated mice differed from controls inasmuch as in their first week of life T cells proliferating in response to TNP were found in the thymus and detected at increased frequencies in the spleen. The frequency of TNP-specific thymocytes and spleen cells declined rapidly, finally reaching in the spleen a level of 20-30% of controls. Furthermore, after antigenic stimulation, the frequency of thymocytes and spleen cells proliferating in response to TNP was found to be increased in control mice, but TNP-specific T cell were no more recovered in the thymus or the spleen of tolerized mice. The same accounted for thymic and splenic T cells proliferating in response to Sp6. They were expanded in control mice after antigenic stimulation, but were undetectable in TNBS-treated mice. Thus, T cells with specificity for an internal (Sp6) and an external (TNP) antigen, provided the latter was present during ontogeny, were detected in the thymus of control and, transiently, in the thymus of tolerized mice. But, the fate of antigen-specific thymocytes was different in prenatally untreated and TNBS-treated mice. The data are interpreted in the sense that tolerance toward non-MHC antigens may be acquired subsequently to tolerance toward self-MHC antigens and possibly after imprinting of antigen specificity.     

Nerve growth factor stimulates axon outgrowth through negative regulation of growth cone actomyosin restraint of microtubule advance

Nerve growth factor (NGF) promotes growth, differentiation, and survival of sensory neurons in the mammalian nervous system. Little is known about how NGF elicits faster axon outgrowth or how growth cones integrate and transform signal input to motor output. Using cultured mouse dorsal root ganglion neurons, we found that myosin II (MII) is required for NGF to stimulate faster axon outgrowth. From experiments inducing loss or gain of function of MII, specific MII isoforms, and vinculin-dependent adhesion-cytoskeletal coupling, we determined that NGF causes decreased vinculin-dependent actomyosin restraint of microtubule advance. Inhibition of MII blocked NGF stimulation, indicating the central role of restraint in directed outgrowth. The restraint consists of myosin IIB- and IIA-dependent processes: retrograde actin network flow and transverse actin bundling, respectively. The processes differentially contribute on laminin-1 and fibronectin due to selective actin tethering to adhesions. On laminin-1, NGF induced greater vinculin-dependent adhesion–cytoskeletal coupling, which slowed retrograde actin network flow (i.e., it regulated the molecular clutch). On fibronectin, NGF caused inactivation of myosin IIA, which negatively regulated actin bundling. On both substrates, the result was the same: NGF-induced weakening of MII-dependent restraint led to dynamic microtubules entering the actin-rich periphery more frequently, giving rise to faster elongation.     

Puberty in a Mesozoic reptile

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