Minipuberty: Looking Back to Understand Moving Forward

Abstract

Hypothalamic-pituitary-gonadal (HPG) axis activation occurs three times in life: the first is during fetal life, and has a crucial role in sex determination, the second time is during the first postnatal months of life, and the third is with the onset of puberty. These windows of activation recall the three windows of the “Developmental Origin of Health and Disease” (DOHaD) paradigm and may play a substantial role in several aspects of human development, such as growth, behavior, and neurodevelopment. From the second trimester of pregnancy there is a peak in gonadotropin levels, followed by a decrease toward term and complete suppression at birth. This is due to the negative feedback of placental estrogens. Studies have shown that in this prenatal HPG axis activation, gonadotropin levels display a sex-related pattern which plays a crucial role in sex differentiation of internal and external genitalia. Soon after birth, there is a new increase in LH, FSH, and sex hormone concentrations, both in males and females, due to HPG re-activation. This postnatal activation is known as “minipuberty.” The HPG axis activity in infancy demonstrates a pulsatile pattern with hormone levels similar to those of true puberty. We review the studies on the changes of these hormones in infancy and their influence on several aspects of future development, from linear growth to fertility and neurobehavior.

Trace Element Interactions, Inflammatory Signaling, and Male Sex Implicated in Reduced Growth Following Excess Oral Iron Supplementation in Pre-Weanling Rats

“…In adults, differences in iron requirements between sexes are largely due to the blood loss of menstruation, where males tend to have higher liver iron stores and hepcidin expression than females [ 81 ]. During infancy, a “mini-puberty” takes place: the hypothalamic-pituitary-gonadal (HPG) is activated leading to a surge of testosterone in male infants [ 84 ]. Testosterone has been shown to inhibit hepcidin transcription and stimulate iron absorption, which in the context of the current study may increase the risk of excess iron exposure [ 85 ].…”

CHARGE syndrome presenting with persistent hypoglycemia: case report and overview of the main genetic syndromes associated with neonatal hypoglycemia

“…Subsequently, blood glucose levels were kept in range through frequent feedings. The in-depth endocrinological examinations performed showed poor cortisol response to the hypoglycemic stimulus (cortisol 7 ng/ml with glucose 28 mg/dl; expected value >18 ng/ml), normal ACTH (12.3 ng/L) and GH values (37.6 ng/ml during hypoglycemia; 9.38 ng/ml random), and adequate thyroid function, while gonadotropins and estrogens appeared inappropriately low for the minipuberty phase [ 5 ]. In view of the suspected hypoadrenalism, oral hydrocortisone therapy (7 mg/m 2 /die) was initiated at 1 week of life, with a subsequent progressive improvement of glucose profile.…”

Biology and postnatal development of organ systems of cynomolgus monkeys (Macaca fascicularis)

“…The pituitary gland initiates and orchestrates other key neuroendocrine activities such as the hypothalamic–pituitary‐gonadal (HPG) axis. In humans, HPG axis activation occurs three times in life 51 . The first occurs in the second trimester of fetal life which may be crucial for sex determination.…”

“…Mini‐puberty is described in animal species including rodents and NHPs; onset in NHPs occurs at approximately 4 months after birth 52,53 . High plasma levels of testosterone, 5α‐dihydrotestosterone and/or estradiol‐17β are detected in CMs during the first 1–4 months after birth which correlates with mini‐puberty in humans 33,51,53 …”

“…52,53 High plasma levels of testosterone, 5α-dihydrotestosterone and/or estradiol-17β are detected in CMs during the first 1-4 months after birth which correlates with mini-puberty in humans. 33,51,53 In CMs, the HPG axis may become fully functional by 4 years of age. Estrogen receptors (ER) and progesterone receptors (PR) are weakly expressed in prepubertal neurons of the female hypothalamus; however, they are abundantly expressed in mid-pubertal neurons (48-52 months) and adult neurons.…”