Impact of Neonatal Hypothyroidism on Leydig Cell Number, Plasma, and Testicular Interstitial Fluid Sex Steroids Concentration

Abstract

We have previously demonstrated that neonatal and transient neonatal hypothyroidism modulates Leydig, Sertoli, and germ cell numbers, sex steroids and androgen binding protein concentration. The present study was undertaken to study the effect of neonatal onset hypothyroidism on Leydig and peritubular myoid cell numbers, plasma and testicular interstitial fluid (TIF) sex steroid concentration at different age groups of Wistar rats. Hypothyroidism was induced by giving 0.05% methimazole (MMI) to lactating mothers or directly to the male pups from day 1 postpartum through days 10, 15, 30, 40 and 60 postpartum. To confirm hypothyroidism, plasma thyroid hormones and TSH were assayed. Plasma and TIF testosterone, progesterone, dihydrotestosterone (DHT) and estradiol were assayed by radioimmunoassay. Leydig cell number in hypothyroid rats were less than the age-matched controls. The diameter of Leydig cells in hypothyroid rats was smaller than the controls but 10 days old hypothyroids alone had larger than control rats. A significant decrease of peritubular myoid cell number was observed in 30, 40 and 60 days hypothyroid rats and increased in 10 and 15 days hypothyroidism. Hypothyroid rats had elevated level of plasma LH and decreased GH (except day 10 postpartum). Plasma PRL level was increased in 10 and 15 days hypothyroid rats and an opposite effect was observed in 40 and 60 days hypothyroidism. Plasma testosterone, DHT and estradiol were decreased in all hypothyroid rats. However, plasma progesterone level in hypothyroid rats was significantly higher at days 10, 30, and 40 postpartum and an opposite effect was seen in 15 and 60 days experimental groups. TIF testosterone and progesterone titre showed a consistent decrease in hypothyroid rats irrespective of the duration. In hypothyroid rats, TIF DHT levels decreased significantly in days 10, 40 and 60 postpartum. However, it increased in days 15 and 30 postpartum. Except at day 10 postpartum, the level of TIF estradiol in hypothyroid rats was significantly less than their age matched controls. Our data clearly indicate that neonatal onset hypothyroidism adversely affect Leydig cell proliferation along with impaired steroidogenesis.

Thyroid Hormones: Their Role in Testicular Steroidogenesis

“…Recent studies showed that neonatal hypothyroidism decreased the Leydig cell number and increased the mesenchymal=peritubular cells. The opposite trend was observed in T3-induced hyperthyroid rats [68,72,95]. These observations suggest that T3 stimulates the differentiation of mesenchymal cells into Leydig cells.…”

“…Kalland et al [48] and Cristovao et al [32] found no change in serum testosterone in prepubertal and adult hypothyroid rats, but 376 R. R. M. Maran most reports showed serum T and E2 levels to be low in hypothyroid rats and rams, while an opposite effect was observed in hyperthyroid animals [15, 24-26, 35, 63, 67, 68, 85, 98]. Recently, we reported that low levels of T, DHT, and E2 were found in the plasma and testicular interstitial fluid (TIF) of hypothyroid rats whose hypothyroidism was induced neonatally [68]. Progesterone levels were also decreased in the TIF, while plasma progesterone levels depended on the duration of hypothyroidism [68].…”

“…Recently, we reported that low levels of T, DHT, and E2 were found in the plasma and testicular interstitial fluid (TIF) of hypothyroid rats whose hypothyroidism was induced neonatally [68]. Progesterone levels were also decreased in the TIF, while plasma progesterone levels depended on the duration of hypothyroidism [68]. Transient neonatal hypothyroidism had unaltered serum and LH-induced androstenedione, progesterone, 17-OH progesterone, and T secretion by whole testis [28,38,50,73], but a decrease in LH-induced T, androstenedione, progesterone, and 17-OH progesterone production by Leydig cells was observed [38,73].…”

Understanding the role of thyroid hormone in Sertoli cell development: a mechanistic hypothesis

“…Nevertheless, a critical development was the report that thyroid hormone receptors are present in high quantities in neonatal Sertoli cells, indicating that the developing Sertoli cell and testis may be an important thyroid hormone target, even though the adult testis is less dependent (Palmero et al 1988;Jannini et al 1990). For example, hypothyroidism in the neonatal rat impairs testicular growth, germ cell maturation, seminiferous tubule lumen formation, and other developmental events (Palmero et al 1989;Francavilla et al 1991;De Franca et al 1995;Maran et al 2001). Despite the inhibitory effects of hypothyroidism on testicular development, rat pups that are made hypothyroid by the administration of the goitrogen 6-propyl-2-thiouracil (PTU) from birth to day 25 postnatal and then allowed to recover back to a euthyroid state have increases in adult testis size and daily sperm production (DSP) of 80% and 140%, respectively, compared with control animals .…”

Propylthiouracil-induced hypothyroidism delays apoptosis during the first wave of spermatogenesis

“…This differentiation involves the induction of the cyclin-dependent kinase inhibitor p27 kip1 by the thyroid hormone (T3) (Holsberger et al, 2005a;Holsberger et al, 2003). Hypothyroidism in the neonatal rat impairs testicular growth, germ cell maturation, seminiferous tubule formation and other differentiation processes (De Franca et al, 1995;Maran et al, 2001). Despite the inhibitory effects induced by goitrogen 6-propyl-2-thiouracil (PTU) when administered from birth to postnatal day 25, a dramatic recovery of thyroid hormone levels to the euthyroid state after postnatal day 45 has been observed (Cooke et al, 1991).…”